Hormones & Cancer最新文献

{"title":"Lower Circulating Androgens Are Associated with Overall Cancer Risk and Prostate Cancer Risk in Men Aged 25-84 Years from the Busselton Health Study.","authors":"Yi X Chan,&nbsp;Matthew W Knuiman,&nbsp;Mark L Divitini,&nbsp;David J Handelsman,&nbsp;John P Beilby,&nbsp;Bu B Yeap","doi":"10.1007/s12672-018-0346-5","DOIUrl":"https://doi.org/10.1007/s12672-018-0346-5","url":null,"abstract":"<p><p>Androgens, notably testosterone (T), have been implicated in development of several common cancers and prostate cancer; however, precise mechanisms remain unclear. This study assessed prospective associations of serum T, dihydrotestosterone (DHT) and estradiol (E2) with overall cancer (excluding skin cancer), prostate, colorectal and lung cancer risk in 1574 community-dwelling men aged 25-84 years. Sex hormones were assayed using mass spectrometry and men were followed for 20 years with outcomes ascertained using data linkage. Over 20 years, there were 289, 116, 48 and 22 men who developed any cancer, prostate cancer, colorectal cancer and lung cancer, respectively. Androgens in the lowest quartile were associated with an increased overall cancer risk (HR = 1.36, 95% CI 1.05-1.76, p = 0.020 for T; and HR = 1.30, 95% CI 1.00-1.69, p = 0.049 for DHT comparing the lowest vs other quartiles). T in the lowest quartile was associated with an increased risk of prostate cancer (HR = 1.53, 95% CI 1.02-2.29, p = 0.038 comparing the lowest vs other quartiles). The association between androgens and overall cancer risk remained similar after excluding prostate cancer outcomes; however, results were not significant. There were no associations of T, DHT or E2 with colorectal or lung cancer risk; however, LH in the highest quartile was associated with an increased risk of lung cancer (HR = 4.55, 95% CI 1.70-12.19, p = 0.003 for the highest vs other quartiles). Whether T is a biomarker of poor health in men with any cancer or prostate cancer requires further confirmation as does the nature and mechanism of the association of a high LH with future lung cancer.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 6","pages":"391-398"},"PeriodicalIF":3.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0346-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223747","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":"Mammographic Density and Circulating Sex Hormones: a Cross-Sectional Study in Postmenopausal Korean Women.","authors":"Kayoung Lee,&nbsp;Jung Eun Yoo,&nbsp;Tuong Linh Nguyen,&nbsp;John Llewelyn Hopper,&nbsp;Yun-Mi Song","doi":"10.1007/s12672-018-0344-7","DOIUrl":"https://doi.org/10.1007/s12672-018-0344-7","url":null,"abstract":"<p><p>Mammographic density (MD) is a strong independent risk factor for breast cancer. It has been suggested that breast cancer is related to the exposure to circulating sex hormones. However, relations between MD and hormones have been inconsistent. In addition, such relations are mainly evaluated in Western populations. Therefore, we conducted a cross-sectional study in 396 cancer-free postmenopausal Korean women who had never used hormone replacement therapy. We assayed estradiol, testosterone, and sex hormone-binding globulin (SHBG) levels. We then calculated free testosterone (cFT) levels. Total and dense areas of digital mammogram were measured using a computer-assisted thresholding method, and non-dense area and percent dense area were calculated. Linear mixed model was used for analyses. Estradiol and testosterone levels were not associated with any MD measures after adjusting for reproductive factors and body mass index. However, cFT was persistently associated with non-dense area even after adjusting for covariates, with non-dense area increased by 3.5% per 1 standard deviation increase of cFT. SHBG showed an inverse association with non-dense area, although it showed a positive association with dense area and percent dense area regardless of adjustment for covariates. Non-dense area was decreased by 5.6% while percent dense area was increased by 13.4% per 1 standard deviation increase of SHBG. These findings suggest that SHBG might be related with breast cancer risk, probably through its association with breast density.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 6","pages":"383-390"},"PeriodicalIF":3.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0344-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846962","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":"Insulin Receptor Substrate Suppression by the Tyrphostin NT157 Inhibits Responses to Insulin-Like Growth Factor-I and Insulin in Breast Cancer Cells.","authors":"Yuzhe Yang,&nbsp;Jie Ying Chan,&nbsp;Nuri A Temiz,&nbsp;Douglas Yee","doi":"10.1007/s12672-018-0343-8","DOIUrl":"https://doi.org/10.1007/s12672-018-0343-8","url":null,"abstract":"<p><p>Insulin and insulin-like growth factor (IGF) signaling systems regulate breast cancer growth, progression, and metastasis. The insulin receptor substrates 1 and 2 (IRS1/2) transduce signaling from the type I IGF receptor (IGF-IR) and insulin receptor (InR) to mediate the biological effects of receptor activation. In breast cancer, IRS-1 plays a critical role in cancer cell proliferation while IRS-2 is associated with motility and metastasis. NT157, a small-molecule tyrphostin, downregulates IRS proteins in several model systems. In breast cancer cells, NT157 treatment suppressed IRS protein expression in a dose-dependent manner. Exposure to NT157 inhibited the activation of downstream signaling mediated by the IRS proteins. NT157 induced a MAPK-dependent serine phosphorylation of IRS proteins which resulted in disassociation between IRS proteins and their receptors resulting in IRS degradation. In estrogen receptor-α-positive (ERα+) breast cancer cells (MCF-7 and T47D), NT157 also resulted in cytoplasmic ERα downregulation likely because of disruption of an IRS-1-IGF-IR/InR/ERα complex. NT157 decreased S phase fraction, monolayer, and anchorage-independent growth after IGF/insulin treatment in ERα+ breast cancer cells. NT157 downregulation of IRS protein expression also sensitized ERα+ breast cancer cells to rapamycin. Moreover, NT157 inhibited the growth of tamoxifen-resistant ERα+ breast cancer cells. Given that both IGF-IR and InR play a role in cancer biology, targeting of IRS adaptor proteins may be a more effective strategy to inhibit the function of these receptors.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"371-382"},"PeriodicalIF":3.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0343-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36499213","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":"Impact of Gender and Age on the Prognosis of Differentiated Thyroid Carcinoma: a Retrospective Analysis Based on SEER.","authors":"Dan Zhang,&nbsp;Jianing Tang,&nbsp;Deguang Kong,&nbsp;Qiuxia Cui,&nbsp;Kun Wang,&nbsp;Yan Gong,&nbsp;Gaosong Wu","doi":"10.1007/s12672-018-0340-y","DOIUrl":"https://doi.org/10.1007/s12672-018-0340-y","url":null,"abstract":"<p><p>The incidence of thyroid cancer in females is significantly higher than that in males; however, females are more likely to have more favorable outcomes. We aimed to determine the characteristics of differentiated thyroid carcinoma (DTC) subtypes in males and females, and to compare their clinical behavior and survival. A total of 68,337 cases were recruited from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. The disease-specific survival (DSS) of follicular variant papillary thyroid carcinoma (FVPTC) and follicular thyroid carcinoma (FTC) were similar to that of classical variant papillary thyroid carcinoma (CPTC) in male patients (FVPTC vs. CPTC, adjusted hazard ratio (aHR) = 0.947, P = 0.776; FTC vs. CPTC, aHR = 1.512, P = 0.104). In premenopausal female (< 55 years old), FVPTC had better DSS than CPTC (aHR = 0.321, P = 0.038) while FTC had worse DSS than CPTC (aHR = 3.272, P = 0.013); in postmenopausal female, FTC had poorer prognosis than CPTC (aHR = 2.145, P = 0.002), no statistical difference was found between CPTC and FVPTC (aHR = 0.724, P = 0.087). For patients younger than 55 years, women had significantly better DSS compared with men with CPTC (aHR = 0.376, P < 0.001) and FVPTC (aHR = 0.102, P < 0.001). However, no difference was observed in patients older than 55 years. Interestingly, outcomes of FTC were not affected by gender in patients of all ages. These results suggested that different clinical behaviors and outcomes of DTC subtypes should be considered in patients with different genders.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 5","pages":"361-370"},"PeriodicalIF":3.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0340-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223749","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":"Nano-Diamino-Tetrac (NDAT) Enhances Resveratrol-Induced Antiproliferation by Action on the RRM2 Pathway in Colorectal Cancers.","authors":"André Wendindondé Nana,&nbsp;Szu Yuan Wu,&nbsp;Yu-Chen Sh Yang,&nbsp;Yu-Tang Chin,&nbsp;Tsai-Mu Cheng,&nbsp;Yih Ho,&nbsp;Wen-Shan Li,&nbsp;Yu-Min Liao,&nbsp;Yi-Ru Chen,&nbsp;Ya-Jung Shih,&nbsp;Yun-Ru Liu,&nbsp;Jens Pedersen,&nbsp;Sandra Incerpi,&nbsp;Aleck Hercbergs,&nbsp;Leroy F Liu,&nbsp;Jacqueline Whang-Peng,&nbsp;Paul J Davis,&nbsp;Hung-Yun Lin","doi":"10.1007/s12672-018-0334-9","DOIUrl":"https://doi.org/10.1007/s12672-018-0334-9","url":null,"abstract":"<p><p>Cancer resistance to chemotherapeutic agents is a major issue in the management of cancer patients. Overexpression of the ribonucleotide reductase regulatory subunit M2 (RRM2) has been associated with aggressive cancer behavior and chemoresistance. Nano-diamino-tetrac (NDAT) is a nanoparticulate derivative of tetraiodothyroacetic acid (tetrac), which exerts anticancer properties via several mechanisms and downregulates RRM2 gene expression in cancer cells. Resveratrol is a stilbenoid phytoalexin which binds to a specific site on the cell surface integrin αvβ3 to trigger cancer cell death via nuclear translocation of COX-2. Here we report that resveratrol paradoxically activates RRM2 gene expression and protein translation in colon cancer cells. This unanticipated effect inhibits resveratrol-induced COX-2 nuclear accumulation. RRM2 downregulation, whether achieved by RNA interference or treatment with NDAT, enhanced resveratrol-induced COX-2 gene expression and nuclear uptake which is essential to integrin αvβ3-mediated-resveratrol-induced antiproliferation in cancer cells. Elsewhere, NDAT downregulated resveratrol-induced RRM2 expression in vivo but potentiated the anticancer effect of the stilbene. These findings suggest that RRM2 appears as a cancer cell defense mechanism which can hinder the anticancer effect of the stilbene via the integrin αvβ3 axis. Furthermore, the antagonistic effect of RRM2 against resveratrol is counteracted by the administration of NDAT.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 5","pages":"349-360"},"PeriodicalIF":3.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0334-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846960","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":"RAGE and Its Ligands: Molecular Interplay Between Glycation, Inflammation, and Hallmarks of Cancer-a Review.","authors":"Gowri Palanissami,&nbsp;Solomon F D Paul","doi":"10.1007/s12672-018-0342-9","DOIUrl":"https://doi.org/10.1007/s12672-018-0342-9","url":null,"abstract":"<p><p>Risk of cancer especially of colon, breast, and pancreas is high in diabetic and obese patients, with potential involvement of augmented expression of RAGE (receptor for advanced glycation end products) and its ligands, namely AGEs (advanced glycation end products), HMGB1 (high-mobility group box 1 protein), and S100 group of proteins. Studies have reported the involvement of RAGE activation by its ligands in growth and survival of cancers, including metastasis and poor prognosis. We propose that this receptor-ligand axis provides the molecular link between certain pre-existing states as hypoxia, hyperglycemia, glycation, inflammation, oxidative stress, and onset of cancers. The chronic inflammatory, hyperglycemic milieu accompanied by glycoxidative stress as in diabetes and obesity, concomitant with the formation of RAGE ligands, instigates RAGE and cancer stem cells, leading to the oncogenic transformation of normal and pre-malignant tissues towards development of neoplasms. We have aimed to elucidate the complete signalling map initiated upon RAGE-ligand splicing, from oncogenesis to progression, epithelial-mesenchymal transition, invasion, cancer stem cell renewal, chemo-resistance, and cancer relapse. We have attributed the complex molecular functions of RAGE-ligand signalling cues to every aspect of cancer promotion, explaining the central network in bridging glycation, inflammation, oxidation, and the hallmarks of cancer. Underlining the substantial requisite for anti-neoplastic agents targeting RAGE and its ligands, we have explicitly discoursed RAGE and its allied components (AGEs, soluble RAGE, RAGE gene polymorphisms) as potential diagnostic and prognostic biomarkers for prompt detection of cancers and implication in impending RAGE-ligand directed, novel combinatorial, and targeted onco-therapeutics.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 5","pages":"295-325"},"PeriodicalIF":3.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0342-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223750","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":"RNA Sequencing of Carboplatin- and Paclitaxel-Resistant Endometrial Cancer Cells Reveals New Stratification Markers and Molecular Targets for Cancer Treatment.","authors":"Raffaele Hellweg, Ashley Mooneyham, Zenas Chang, Mihir Shetty, Edith Emmings, Yoshie Iizuka, Christopher Clark, Timothy Starr, Juan H Abrahante, Florian Schütz, Gottfried Konecny, Peter Argenta, Martina Bazzaro","doi":"10.1007/s12672-018-0337-6","DOIUrl":"10.1007/s12672-018-0337-6","url":null,"abstract":"<p><p>Despite advances in surgical technique and adjuvant treatment, endometrial cancer has recently seen an increase in incidence and mortality in the USA. The majority of endometrial cancers can be cured by surgery alone or in combination with adjuvant chemo- or radiotherapy; however, a subset of patients experience recurrence for reasons that remain unclear. Recurrence is associated with chemoresistance to carboplatin and paclitaxel and consequentially, high mortality. Understanding the pathways involved in endometrial cancer chemoresistance is paramount for the identification of biomarkers and novel molecular targets for this disease. Here, we generated the first matched pairs of carboplatin-sensitive/carboplatin-resistant and paclitaxel-sensitive/paclitaxel-resistant endometrial cancer cells and subjected them to bulk RNA sequencing analysis. We found that 45 genes are commonly upregulated in carboplatin- and paclitaxel-resistant cells as compared to controls. Of these, the leukemia inhibitory factor, (LIF), the protein tyrosine phosphatase type IVA, member 3 (PTP4A3), and the transforming growth factor beta 1 (TGFB1) showed a highly significant correlation between expression level and endometrial cancer overall survival (OS) and can stratify the 545 endometrial cancer patients in the TCGA cohort into a high-risk and low-risk-cohorts. Additionally, four genes within the 45 upregulated chemoresistance-associated genes are ADAMTS5, MICAL2, STAT5A, and PTP4A3 codes for proteins for which small-molecule inhibitors already exist. We identified these proteins as molecular targets for chemoresistant endometrial cancer and showed that treatment with their correspondent inhibitors effectively killed otherwise chemoresistant cells. Collectively, these findings underline the utility of matched pair of chemosensitive and chemoresistant cancer cells to identify markers for endometrial cancer risk stratification and to serve as a pharmacogenomics model for identification of alternative chemotherapy approaches for treatment of patients with recurrent disease.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 5","pages":"326-337"},"PeriodicalIF":3.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10355894/pdf/12672_2018_Article_337.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851442","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":"Increased High Molecular Weight FGF2 in Endocrine-Resistant Breast Cancer.","authors":"Ana Sahores,&nbsp;Virginia Figueroa,&nbsp;María May,&nbsp;Marcos Liguori,&nbsp;Adrián Rubstein,&nbsp;Cynthia Fuentes,&nbsp;Britta M Jacobsen,&nbsp;Andrés Elía,&nbsp;Paola Rojas,&nbsp;Gonzalo R Sequeira,&nbsp;Michelle M Álvarez,&nbsp;Pedro González,&nbsp;Hugo Gass,&nbsp;Stephen Hewitt,&nbsp;Alfredo Molinolo,&nbsp;Claudia Lanari,&nbsp;Caroline A Lamb","doi":"10.1007/s12672-018-0339-4","DOIUrl":"https://doi.org/10.1007/s12672-018-0339-4","url":null,"abstract":"<p><p>Endocrine resistance may develop as a consequence of enhanced growth factor signaling. Fibroblast growth factor 2 (FGF2) consists of a low and several high molecular weight forms (HMW-FGF2). We previously demonstrated that antiprogestin-resistant mammary carcinomas display lower levels of progesterone receptor A isoforms (PRA) than B isoforms (PRB). Our aim was to evaluate the role of FGF2 isoforms in breast cancer progression. We evaluated FGF2 expression, cell proliferation, and pathway activation in models with different PRA/PRB ratios. We performed lentiviral infections of different FGF2 isoforms using the human hormone-responsive T47D-YA cells, engineered to only express PRA, and evaluated tumor growth, metastatic dissemination, and endocrine responsiveness. We assessed FGF2 expression and localization in 81 human breast cancer samples. Antiprogestin-resistant experimental mammary carcinomas with low PRA/PRB ratios and T47D-YB cells, which only express PRB, displayed higher levels of HMW-FGF2 than responsive variants. HMW-FGF2 overexpression in T47D-YA cells induced increased tumor growth, lung metastasis, and antiprogestin resistance compared to control tumors. In human breast carcinomas categorized by their PRA/PRB ratio, we found nuclear FGF2 expression in 55.6% of tumor cells. No differences were found between nuclear FGF2 expression and Ki67 proliferation index, tumor stage, or tumor grade. In low-grade tumor samples, moderate to high nuclear FGF2 levels were associated to carcinomas with low PRA/PRB ratio. In conclusion, we show that HMW-FGF2 isoforms are PRB targets which confer endocrine resistance and are localized in the nuclei of breast cancer samples. Hence, targeting intracellular FGF2 may contribute to overcome tumor progression.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 5","pages":"338-348"},"PeriodicalIF":3.0,"publicationDate":"2018-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0339-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10228185","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 Impact of ESR1 Mutations on the Treatment of Metastatic Breast Cancer.","authors":"Sasha M Pejerrey,&nbsp;Derek Dustin,&nbsp;Jin-Ah Kim,&nbsp;Guowei Gu,&nbsp;Yassine Rechoum,&nbsp;Suzanne A W Fuqua","doi":"10.1007/s12672-017-0306-5","DOIUrl":"https://doi.org/10.1007/s12672-017-0306-5","url":null,"abstract":"<p><p>After nearly 20 years of research, it is now established that mutations within the estrogen receptor (ER) gene, ESR1, frequently occur in metastatic breast cancer and influence response to hormone therapy. Though early studies presented differing results, sensitive sequencing techniques now show that ESR1 mutations occur at a frequency between 20 and 40% depending on the assay method. Recent studies have focused on several \"hot spot mutations,\" a cluster of mutations found in the hormone-binding domain of the ESR1 gene. Throughout the course of treatment, tumor evolution can occur, and ESR1 mutations emerge and become enriched in the metastatic setting. Sensitive techniques to continually monitor mutant burden in vivo are needed to effectively treat patients with mutant ESR1. The full impact of these mutations on tumor response to different therapies remains to be determined. However, recent studies indicate that mutant-bearing tumors may be less responsive to specific hormonal therapies, and suggest that aromatase inhibitor (AI) therapy may select for the emergence of ESR1 mutations. Additionally, different mutations may respond discretely to targeted therapies. The need for more preclinical mechanistic studies on ESR1 mutations and the development of better agents to target these mutations are urgently needed. In the future, sequential monitoring of ESR1 mutational status will likely direct personalized therapeutic regimens appropriate to each tumor's unique mutational landscape.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 4","pages":"215-228"},"PeriodicalIF":3.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-017-0306-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9851440","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":"Adiposity Results in Metabolic and Inflammation Differences in Premenopausal and Postmenopausal Women Consistent with the Difference in Breast Cancer Risk.","authors":"H Zhao,&nbsp;J Wang,&nbsp;D Fang,&nbsp;O Lee,&nbsp;R T Chatterton,&nbsp;V Stearns,&nbsp;S A Khan,&nbsp;S E Bulun","doi":"10.1007/s12672-018-0329-6","DOIUrl":"https://doi.org/10.1007/s12672-018-0329-6","url":null,"abstract":"<p><p>Obesity is associated with increased risk of breast cancer in postmenopausal but not in premenopausal women. Many factors may be responsible for this difference. The aim of this study was to determine the mechanisms by which the genes related to the AMPK pathway, inflammation, and estrogen actions are affected by adiposity in breast tissue with the objective of identifying differences that may explain the different breast cancer risk in premenopausal and postmenopausal women. Random fine needle aspirates (rFNAs) of breast tissue were collected from 57 premenopausal and 55 postmenopausal women and were classified as normal weight, overweight, or obese. Expression levels of 21 target genes were determined using a TaqMan Low Density Array procedure. Breast tissue estradiol levels were measured by a liquid chromatography-tandem mass spectrometry procedure, and serum estradiol and follicle-stimulating hormone (FSH) were measured by a radioimmunoassay and an enzyme-linked immunosorbent assay, respectively. We found that in postmenopausal women, serum and tissue estradiol levels were increased in those who were overweight, and serum FSH levels were decreased in obese status. Interestingly, RPS6KB1, an AMPK downstream-responsive gene for protein synthesis and cell growth, and estrogen receptor α (encoded by the ESR1 gene) and its target gene GATA3 were significantly decreased in rFNA of premenopausal, obese women. In postmenopausal women, RPS6KB1, ESR1, and GATA3 expression remained unchanged in relation to adiposity. However, prostaglandin-endoperoxide synthase 2 (PTGS2), cyclin D1 (CCND1), and another ESR1 target gene, TFF1, were elevated in rFNA of obese postmenopausal women. Thus, as bodyweight increases, gene expression is indicative of increased proliferation in postmenopausal women but decreased proliferation in premenopausal women. Overall, our data reveal a novel process by which obesity promotes the risk of breast cancer in postmenopausal but not premenopausal women.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 4","pages":"229-239"},"PeriodicalIF":3.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0329-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10281513","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}