Hormones & Cancer最新文献

{"title":"Expression of Genes for Methylxanthine Pathway-Associated Enzymes Accompanied by Sex Steroid Receptor Status Impacts Breast Carcinoma Progression.","authors":"James L Wittliff,&nbsp;Seth B Sereff,&nbsp;Michael W Daniels","doi":"10.1007/s12672-017-0309-2","DOIUrl":"https://doi.org/10.1007/s12672-017-0309-2","url":null,"abstract":"<p><p>Consumption of methylxanthine alkaloids appears to induce activities by antagonizing adenosine receptors, implicated in breast cancer behavior in vitro. Our goal was to evaluate expression of genes for methylxanthine receptors and metabolizing enzymes to assess risk of breast carcinoma recurrence. Clinical outcomes, estrogen/progestin receptor results, and gene expression assays guided selection. RNA was isolated from laser capture microdissection-procured carcinoma cells for microarray using established protocols. Gene expression levels of eight methylxanthine receptors, eight metabolizing enzymes, and various phosphodiesterases were retrieved from microarray results. Univariable Cox regressions and Kaplan-Meier plots were determined for each gene with R software. Individually, lower expressions of PDE4A, CYP2A6, or CYP2E were related to decreased progression-free survival (PFS) and overall survival (OS). PDE1A over-expression predicted decreased PFS and OS. ADORA2B and RYR1 over-expressions predicted diminished OS. ER+ cancers exhibited lower ADORA1, ADORA2B, and RYR1 and elevated PDE4A, CYP2A6, and CYP2E expressions. Of PR+ carcinomas, diminished ADORA2B and RYR1 and elevated expressions of ADORA3, PDE4A, CYP2C8, and CYP2E were noted. Least absolute shrinkage and selection operator (LASSO) revealed that CYP2E, PDE1A, and PDE4A expressions collectively predicted PFS whereas ADORA1, CYP2E, PDE1A, PDE1B, and PDE4A expressions jointly predicted OS. Models were clinically significant when validated externally. LASSO also derived a six-gene model and five-gene model that predicted PFS of ER- or PR- carcinomas, respectively. Similarly, five-gene and four-gene models predicted OS in ER- or PR- carcinomas, respectively. Collectively, expression of genes involved in methylxanthine action and metabolism in single-cell types predicted clinical outcomes of breast carcinoma indicating promise for developing diagnostics and design of new therapeutics.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 5-6","pages":"298-313"},"PeriodicalIF":3.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0309-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9837476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Androgen Receptor Supports Tumor Progression After the Loss of Ovarian Function in a Preclinical Model of Obesity and Breast Cancer.","authors":"Elizabeth A Wellberg,&nbsp;L Allyson Checkley,&nbsp;Erin D Giles,&nbsp;Stevi J Johnson,&nbsp;Robera Oljira,&nbsp;Reema Wahdan-Alaswad,&nbsp;Rebecca M Foright,&nbsp;Greg Dooley,&nbsp;Susan M Edgerton,&nbsp;Sonali Jindal,&nbsp;Ginger C Johnson,&nbsp;Jennifer K Richer,&nbsp;Peter Kabos,&nbsp;Ann D Thor,&nbsp;Pepper Schedin,&nbsp;Paul S MacLean,&nbsp;Steven M Anderson","doi":"10.1007/s12672-017-0302-9","DOIUrl":"https://doi.org/10.1007/s12672-017-0302-9","url":null,"abstract":"<p><p>The androgen receptor (AR) has context-dependent roles in breast cancer growth and progression. Overall, high tumor AR levels predict a favorable patient outcome, but several studies have established a tumor promotional role for AR, particularly in supporting the growth of estrogen receptor positive (ER-positive) breast cancers after endocrine therapy. Our previous studies have demonstrated that obesity promotes mammary tumor progression after ovariectomy (OVX) in a rat model of postmenopausal breast cancer. Here, we investigated a potential role for AR in obesity-associated post-OVX mammary tumor progression following ovarian estrogen loss. In this model, we found that obese but not lean rats had nuclear localized AR in tumors that progressed 3 weeks after OVX, compared to those that regressed. AR nuclear localization is consistent with activation of AR-dependent transcription. Longer-term studies (8 weeks post-OVX) showed that AR nuclear localization and expression were maintained in tumors that had progressed, but AR expression was nearly lost in tumors that were regressing. The anti-androgen enzalutamide effectively blocked tumor progression in obese rats by promoting tumor necrosis and also prevented the formation of new tumors after OVX. Neither circulating nor mammary adipose tissue levels of the AR ligand testosterone were elevated in obese compared to lean rats; however, IL-6, which we previously reported to be higher in plasma from obese versus lean rats, sensitized breast cancer cells to low levels of testosterone. Our study demonstrates that, in the context of obesity, AR plays a role in driving ER-positive mammary tumor progression in an environment of low estrogen availability, and that circulating factors unique to the obese host, including IL-6, may influence how cancer cells respond to steroid hormones.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 5-6","pages":"269-285"},"PeriodicalIF":3.0,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0302-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9844602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Complex Biology of the Aryl Hydrocarbon Receptor and Its Role in the Pituitary Gland.","authors":"Robert Formosa,&nbsp;Josanne Vassallo","doi":"10.1007/s12672-017-0300-y","DOIUrl":"https://doi.org/10.1007/s12672-017-0300-y","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor best known for its ability to mediate the effects of environmental toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), polycyclic aromatic hydrocarbons (PAHs), benzene, and polychlorinated biphenyls (PCBs) through the initiation of transcription of a number of metabolically active enzymes. Therefore, the AHR has been studied mostly in the context of xenobiotic signaling. However, several studies have shown that the AHR is constitutively active and plays an important role in general cell physiology, independently of its activity as a xenobiotic receptor and in the absence of exogenous ligands. Within the pituitary, activation of the AHR by environmental toxins has been implicated in disruption of gonadal development and fertility. Studies carried out predominantly in mouse models have revealed the detrimental influence of several environmental toxins on specific cell lineages of the pituitary tissue mediated by activation of AHR and its downstream effectors. Activation of AHR during fetal development adversely affected pituitary development while adult models exposed to AHR ligands demonstrated varying degrees of pituitary dysfunction. Such dysfunction may arise as a result of direct effects on pituitary cells or indirect effects on the hypothalamic-pituitary-gonadal axis. This review offers in-depth analysis of all aspects of AHR biology, with a particular focus on its role and activity within the adenohypophysis and specifically in pituitary tumorigenesis. A novel mechanism by which the AHR may play a direct role in pituitary cell proliferation and tumor formation is postulated. This review therefore attempts to cover all aspects of the AHR's role in the pituitary tissue, from fetal development to adult physiology and the pathophysiology underlying endocrine disruption and pituitary tumorigenesis.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 4","pages":"197-210"},"PeriodicalIF":3.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0300-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9850006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired Tamoxifen Resistance in MCF-7 Breast Cancer Cells Requires Hyperactivation of eIF4F-Mediated Translation.","authors":"Dedra H Fagan,&nbsp;Lynsey M Fettig,&nbsp;Svetlana Avdulov,&nbsp;Heather Beckwith,&nbsp;Mark S Peterson,&nbsp;Yen-Yi Ho,&nbsp;Fan Wang,&nbsp;Vitaly A Polunovsky,&nbsp;Douglas Yee","doi":"10.1007/s12672-017-0296-3","DOIUrl":"https://doi.org/10.1007/s12672-017-0296-3","url":null,"abstract":"<p><p>While selective estrogen receptor modulators, such as tamoxifen, have contributed to increased survival in patients with hormone receptor-positive breast cancer, the development of resistance to these therapies has led to the need to investigate other targetable pathways involved in oncogenic signaling. Approval of the mTOR inhibitor everolimus in the therapy of secondary endocrine resistance demonstrates the validity of this approach. Importantly, mTOR activation regulates eukaryotic messenger RNA translation. Eukaryotic translation initiation factor 4E (eIF4E), a component of the cap-dependent translation complex eIF4F, confers resistance to drug-induced apoptosis when overexpressed in multiple cell types. The eIF4F complex is downstream of multiple oncogenic pathways, including mTOR, making it an appealing drug target. Here, we show that the eIF4F translation pathway was hyperactive in tamoxifen-resistant (TamR) MCF-7L breast cancer cells. While overexpression of eIF4E was not sufficient to confer resistance to tamoxifen in MCF-7L cells, its function was necessary to maintain resistance in TamR cells. Targeting the eIF4E subunit of the eIF4F complex through its degradation using an antisense oligonucleotide (ASO) or via sequestration using a mutant 4E-BP1 inhibited the proliferation and colony formation of TamR cells and partially restored sensitivity to tamoxifen. Further, the use of these agents also resulted in cell cycle arrest and induction of apoptosis in TamR cells. Finally, the use of a pharmacologic agent which inhibited the eIF4E-eIF4G interaction also decreased the proliferation and anchorage-dependent colony formation in TamR cells. These results highlight the eIF4F complex as a promising target for patients with acquired resistance to tamoxifen and, potentially, other endocrine therapies.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 4","pages":"219-229"},"PeriodicalIF":3.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0296-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol Intake and Risk of Breast Cancer by Histologic Subtype and Estrogen Receptor Status Among Women Aged 55 to 74 Years.","authors":"Michelle L Baglia,&nbsp;Kathleen E Malone,&nbsp;Mei-Tzu C Tang,&nbsp;Christopher I Li","doi":"10.1007/s12672-017-0297-2","DOIUrl":"https://doi.org/10.1007/s12672-017-0297-2","url":null,"abstract":"<p><p>Previous studies suggest that alcohol consumption and risk of breast cancer may differ by histologic subtype and hormone receptor status, though results are not entirely consistent. In this population-based case-control study, we evaluated the association between alcohol consumption and risk of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and invasive ductal-lobular carcinoma (IDLC) overall and by estrogen receptor (ER) status, among women aged 55-74 years of age. Using polytomous regression, associations between current alcohol consumption, overall and by type of alcohol, and breast cancer risk were evaluated in 891 controls and 905 IDC, 567 ILC, and 489 IDLC cases. Current alcohol use was moderately associated with risk of ILC (odds ratio = 1.25, 95% confidence interval 0.99, 1.58) with a positive dose-response relationship based on average number of drinks per week consumed (P _trend = 0.0005). When further stratified by ER status, alcohol use was positively associated with risk of ER+ ILC (P _trend = 0.002) and ER+ IDC (P _trend = 0.02), but inversely associated with risk of ER-IDC (P _trend = 0.01). No association between alcohol and risk of IDLC tumors was observed. While the link between alcohol consumption and breast cancer risk is well established, our results suggest that the increased risk associated with alcohol is largely limited to ER+ ILC and ER+ IDC. Thus, avoiding or moderating alcohol consumption may be one way that women can lower their risks of these forms of breast cancer.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"211-218"},"PeriodicalIF":3.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0297-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35048628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Panobinostat Enhances Growth Suppressive Effects of Progestin on Endometrial Carcinoma by Increasing Progesterone Receptor and Mitogen-Inducible Gene-6.","authors":"Hirofumi Ando,&nbsp;Tsutomu Miyamoto,&nbsp;Hiroyasu Kashima,&nbsp;Shotaro Higuchi,&nbsp;Koichi Ida,&nbsp;David Hamisi Mvunta,&nbsp;Tanri Shiozawa","doi":"10.1007/s12672-017-0295-4","DOIUrl":"https://doi.org/10.1007/s12672-017-0295-4","url":null,"abstract":"<p><p>Although progestin has been used to treat endometrial hyperplasia and endometrial carcinoma (EC), its therapeutic efficacy is limited. In order to improve this, the underlining mechanisms of the effects of progestin need to be elucidated in more detail. In the present study, we examined the involvement of mitogen-inducible gene-6 (MIG6), a negative regulator of the EGF receptor, in the progestin-mediated growth suppression of endometrial epithelia. The immunohistochemical expression of MIG6 was elevated in the early to mid-secretory phases of normal endometrium and also with endometrial hyperplasia after medroxyprogesterone acetate (MPA) therapy. The addition of progesterone (P4) to progesterone receptor (PR)-positive EC cells reduced the viability and induced MIG6 messenger RNA (mRNA) and protein expression. The silencing of MIG6 using siRNA eliminated the P4-mediated reduction of EC cell viability, indicating that MIG6 is an essential downstream component of PR-mediated growth suppression. In order to enhance PR-driven signals, we examined the effects of histone deacetylase (HDAC) inhibitors because histone acetylation has been shown to increase the expression of PR. The addition of three HDAC inhibitors (panobinostat, LBH589; trichostatin A, TSA; suberoylanilide hydroxamic acid, SAHA) decreased the viability of EC cells and up-regulated the expression of PR and MIG6, and these effects were the strongest with LBH589. The addition of LBH589 and MPA synergistically decreased the viability and increased apoptosis in EC cells. These results indicate that LBH589 has potential as an enhancer of progestin therapy via the up-regulation of PR and MIG6.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 4","pages":"257-267"},"PeriodicalIF":3.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0295-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9850001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen Receptor-β Modulation of the ERα-p53 Loop Regulating Gene Expression, Proliferation, and Apoptosis in Breast Cancer.","authors":"Wenwen Lu,&nbsp;Benita S Katzenellenbogen","doi":"10.1007/s12672-017-0298-1","DOIUrl":"https://doi.org/10.1007/s12672-017-0298-1","url":null,"abstract":"<p><p>Estrogen receptor α (ERα) is a crucial transcriptional regulator in breast cancer, but estrogens mediate their effects through two estrogen receptors, ERα and ERβ, subtypes that have contrasting regulatory actions on gene expression and the survival and growth of breast cancer cells. Here, we examine the impact of ERβ on the ERα-p53 loop in breast cancer. We found that ERβ attenuates ERα-induced cell proliferation, increases apoptosis, and reverses transcriptional activation and repression by ERα. Further, ERβ physically interacts with p53, reduces ERα-p53 binding, and antagonizes ERα-p53-mediated transcriptional regulation. ERα directs SUV39H1/H2 and histone H3 lys9 trimethylation (H3K9me3) heterochromatin assembly at estrogen-repressed genes to silence p53-activated transcription. The copresence of ERβ in ERα-positive cells abrogates the H3K9me3 repressive heterochromatin conformation by downregulating SUV39H1 and SUV39H2, thereby releasing the ERα-induced transcriptional block. Furthermore, the presence of ERβ stimulates accumulation of histone H3 lys4 trimethylation (H3K4me3) and RNA polymerase II (RNA Pol II) on ERα-repressed genes, inducing H3K4me3-associated epigenetic activation of the transcription of these repressed genes that can promote p53-based tumor suppression. ERβ also reduced corepressor N-CoR and SMRT recruitment by ERα that could attenuate the crosstalk between ERα and p53. Overall, our data reveal a novel mechanism for ERβ's anti-proliferative and pro-apoptotic effects in breast cancer cells involving p53 and epigenetic changes in histone methylation that underlie gene regulation of these cellular activities.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"230-242"},"PeriodicalIF":3.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0298-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35055994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in Androgen-Mediated Cell Viability in Prostate Cancer Cells.","authors":"Cecilia Colombero, Daniela Papademetrio, Paula Sacca, Eduardo Mormandi, Elida Alvarez, Susana Nowicki","doi":"10.1007/s12672-017-0299-0","DOIUrl":"10.1007/s12672-017-0299-0","url":null,"abstract":"<p><p>20-Hydroxyeicosatetraenoic acid (20-HETE) is generated intracellularly through the ω-hydroxylation of arachidonic acid by the cytochrome P450 (in humans, CYP4A11 and CYP4F2). 20-HETE induces mitogenic responses in different cancer cells. The aim of this study was to analyze how 20-HETE impacts cell survival, proliferation, and apoptosis in prostate cancer cells. Incubation of the human androgen-sensitive cells (LNCaP) with 1-10 μM HET0016 (a selective inhibitor of 20-HETE synthesis) reduced cell viability by 49*-64%* (*p < 0.05 vs. control). This was explained by a reduction in cell proliferation (vehicle, 46 ± 3%; 1 μM, 23 ± 3%*; 10 μM, 28 ± 3%*) and by an increase in apoptosis (vehicle, 2.1 ± 0%; 1 μM, 16 ± 4%*; 10 μM, 31 ± 3%*). Furthermore, the increase in LNCaP cell viability induced by dihydrotestosterone (DHT, 0.1 nM) was abrogated by 30*-42%* by 1-10 μM HET0016. Incubation with 20-HETE (5-1000 nM) increased LNCaP cell viability up to 50%*, together with a 70%* reduction in apoptosis. PC-3 (androgen-insensitive) cell viability was not affected by either HET0016 or 20-HETE. In LNCaP cells, HET0016 (10 μM) diminished the expression of androgen receptors (AR): messenger RNA (mRNA) (40%*) and protein (50%*). DHT (10 nM) augmented CYP4F2 protein expression (1.9-fold*) and 20-HETE levels (50%*). Oppositely, enzalutamide (AR antagonist) reduced CYP4F2 mRNA and protein expressions by 30 and 25%, respectively. Thus, intracellular availability of 20-HETE is necessary to sustain LNCaP cell viability. 20-HETE may act as a signaling molecule in the pathways involved in LNCaP cell viability upon stimulation of the AR. This effect may be partially attributed to its role on securing normal AR expression levels that in turn contribute to maintain intracellular levels of 20-HETE.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 4","pages":"243-256"},"PeriodicalIF":3.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10355871/pdf/12672_2017_Article_299.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9850007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth Hormone Receptor Knockdown Sensitizes Human Melanoma Cells to Chemotherapy by Attenuating Expression of ABC Drug Efflux Pumps.","authors":"Reetobrata Basu, Nicholas Baumgaertel, Shiyong Wu, John J Kopchick","doi":"10.1007/s12672-017-0292-7","DOIUrl":"10.1007/s12672-017-0292-7","url":null,"abstract":"<p><p>Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action. We found that GH treatment of human melanoma cells upregulates expression of multiple ABC transporters and increases the EC50 of melanoma drug vemurafenib. Also, vemurafenib-resistant melanoma cells had upregulated levels of GH receptor (GHR) expression as well as ABC efflux pumps. GHR knockdown (KD) using siRNA in human melanoma cells treated with sub-EC50 doses of anti-tumor compounds resulted in significantly increased drug retention, decreased cell proliferation and increased drug efficacy, compared to mock-transfected controls. Our set of findings identify an unknown mechanism of GH regulation in mediating melanoma drug resistance and validates GHR as a unique therapeutic target for sensitizing highly therapy-resistant human melanoma cells to lower doses of anti-cancer drugs.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 3","pages":"143-156"},"PeriodicalIF":3.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10355985/pdf/12672_2017_Article_292.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9844597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of Gonadoblastoma Development in Patients with Turner Syndrome with Cryptic Y Chromosome Material.","authors":"Ahreum Kwon,&nbsp;Sei Eun Hyun,&nbsp;Mo Kyung Jung,&nbsp;Hyun Wook Chae,&nbsp;Woo Jung Lee,&nbsp;Tae Hyuk Kim,&nbsp;Duk Hee Kim,&nbsp;Ho-Seong Kim","doi":"10.1007/s12672-017-0291-8","DOIUrl":"https://doi.org/10.1007/s12672-017-0291-8","url":null,"abstract":"<p><p>Current guidelines recommend that testing for Y chromosome material should be performed only in patients with Turner syndrome harboring a marker chromosome and exhibiting virilization in order to detect individuals who are at high risk of gonadoblastoma. However, cryptic Y chromosome material is suggested to be a risk factor for gonadoblastoma in patients with Turner syndrome. Here, we aimed to estimate the frequency of cryptic Y chromosome material in patients with Turner syndrome and determine whether Y chromosome material increased the risk for development of gonadoblastoma. A total of 124 patients who were diagnosed with Turner syndrome by conventional cytogenetic techniques underwent additional molecular analysis to detect cryptic Y chromosome material. In addition, patients with Turner syndrome harboring Y chromosome cell lines had their ovaries removed prophylactically. Finally, we assessed the occurrence of gonadoblastoma in patients with Turner syndrome. Molecular analysis demonstrated that 10 patients had Y chromosome material among 118 patients without overt Y chromosome (8.5%). Six patients with overt Y chromosome and four patients with cryptic Y chromosome material underwent oophorectomy. Histopathological analysis revealed that the occurrence of gonadoblastoma in the total group was 2.4%, and gonadoblastoma occurred in one of six patients with an overt Y chromosome (16.7%) and 2 of 10 patients with cryptic Y chromosome material (20.0%). The risk of developing gonadoblastoma in patients with cryptic Y chromosome material was similar to that in patients with overt Y chromosome. Therefore, molecular screening for Y chromosome material should be recommended for all patients with Turner syndrome to detect individuals at a high risk of gonadoblastoma and to facilitate proper management of the disease.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"8 3","pages":"166-173"},"PeriodicalIF":3.0,"publicationDate":"2017-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0291-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9847753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}