Hormones & Cancer最新文献

{"title":"Downregulation of IGF1R Expression Inhibits Growth and Enhances Cisplatin Sensitivity of Head and Neck Squamous Cell Carcinoma Cells In Vitro.","authors":"Ashraf Khalil,&nbsp;Mark J Jameson","doi":"10.1007/s12672-018-0352-7","DOIUrl":"https://doi.org/10.1007/s12672-018-0352-7","url":null,"abstract":"<p><p>A lentivirus-mediated doxycycline-inducible pTRIPZ shRNAmir plasmid targeting IGF1R transcript was transfected into two head and neck squamous cell carcinoma (HNSCC) cell lines to silence IGF1R expression and to assess the effect of its downregulation on cisplatin sensitivity in vitro. In Cal27-regIGF1R and SCC25-regIGF1R cell lines, IGF1R protein expression was reduced by more than 90% after 72 h of incubation with doxycycline. Both basal and IGF-stimulated pIGF1R, pAKT, and pERK were significantly reduced, without influence on total AKT and ERK expression. Downregulation of the IGF1R was associated with decreased proliferation and cell viability in both cell lines. Reduced IGF1R expression was also associated with increased sub-G0/G1-phase and G0/G1-phase populations and decreased S-phase and G2/M-phase populations. IGF1R downregulation enhanced sensitivity to cisplatin with decrease of cisplatin IC₅₀ from 15 to 7.1 in Cal27-regIGF1R cells and from 11 to 6.3 in SCC25-regIGF1R cells. Cisplatin exhibited increased pro-apoptotic activity by annexin V staining and PARP cleavage in both cells lines when cultured in doxycycline. Thus, in two HNSCC cell lines in vitro, reduced IGF1R expression results in reduced growth rate and increased sensitivity to cisplatin. Thus, IGF1R downregulation and/or inhibition may serve as a useful adjunct to platinum-based cytotoxic chemotherapy.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 1","pages":"11-23"},"PeriodicalIF":3.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0352-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205103","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":"Familial Cancer Clustering in Patients with Prolactinoma.","authors":"Sandra Pekic,&nbsp;Ivan Soldatovic,&nbsp;Dragana Miljic,&nbsp;Marko Stojanovic,&nbsp;Mirjana Doknic,&nbsp;Milan Petakov,&nbsp;Vera Popovic","doi":"10.1007/s12672-018-0348-3","DOIUrl":"https://doi.org/10.1007/s12672-018-0348-3","url":null,"abstract":"<p><p>People are at higher risk for malignancy as they get older or have a strong family history of cancer. This study aims to collect family history of cancer in a large cohort of patients with pituitary adenomas (PA) in outpatient clinic from years 2005-2017. Overall, 46.6% of 1062 patients with PA had a family member affected with cancer. Breast cancer in family members was reported in 15.3% of patients with prolactinomas which was significantly higher than in families of patients with non-functioning pituitary adenomas (NFPA) (10.0%) or acromegaly (6.8%) (p = 0.004). Lung cancer in family members was reported in 12.1% of patients with prolactinomas, significantly higher than in families of NFPA patients (7.0%, p = 0.049). Colorectal cancer in relatives of patients with PA was reported with any type of PA. Furthermore, patients with a positive family history of malignancy were diagnosed with PA at an earlier age than patients with a negative family history (43.6 ± 15.9 vs 46.0 ± 16.4 years, p = 0.015). Female patients with prolactinoma are more commonly diagnosed before the age of 25 years. Forty-two percent of patients with PA diagnosed before the age of 25 years had a second- and third-degree relative with cancer, significantly higher than patients with PA diagnosed later in life (25.8%, p &lt; 0.001). Breast, lung, and colon cancers in second- and third-degree relatives were reported in significantly higher proportion of patients with PA diagnosed before the age of 25 years, compared with patients with PA diagnosed later in life (breast cancer: 10.9 vs 6.1%, p = 0.033; lung cancer: 10.9 vs 5.8%, p = 0.02; colon cancer: 9.5 vs 4.0%, p = 0.004). These results suggest familial cancer clustering in patients with prolactinoma and young patients with PA (younger than 25 years at diagnosis of PA). In particular, there is a strong association between prolactinoma and family history of breast and lung cancers. Further research of possible shared genetic susceptibility of prolactinoma and breast and lung cancers is needed.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 1","pages":"45-50"},"PeriodicalIF":3.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0348-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223751","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":"Chilean Registry for Neuroendocrine Tumors: A Latin American Perspective.","authors":"Mauricio P Pinto,&nbsp;Matías Muñoz Medel,&nbsp;Diego Carrillo,&nbsp;Ignacio N Retamal,&nbsp;M Loreto Bravo,&nbsp;Yasna Valenzuela,&nbsp;Bruno Nervi,&nbsp;César Sánchez,&nbsp;Héctor Galindo,&nbsp;Carolina Ibañez,&nbsp;José Peña,&nbsp;Carlos Balmaceda,&nbsp;Jorge Madrid,&nbsp;Juan Briones,&nbsp;Javiera Torres,&nbsp;Flavia Nilo,&nbsp;Francisco J Guarda,&nbsp;Juan Carlos Quintana,&nbsp;Pilar Orellana,&nbsp;Sebastián Mondaca,&nbsp;Francisco Acevedo,&nbsp;Daniel Vicentini,&nbsp;Miguel Cordova-Delgado,&nbsp;Gareth I Owen,&nbsp;Marcelo Garrido","doi":"10.1007/s12672-018-0354-5","DOIUrl":"https://doi.org/10.1007/s12672-018-0354-5","url":null,"abstract":"<p><p>Neuroendocrine tumors (NETs) are relatively rare and highly heterogeneous neoplasms. Despite this, recent studies from North America and Central Europe have suggested an increase in incidence. In Latin America, NET data are scarce and scattered with only a few studies reporting registries. Our goal was to establish a NET registry in Chile. Here, we report the establishment and our first 166 NET patients. We observed a slight preponderance of males, a median age at diagnosis of 53 years and a median overall survival of 110 months. As anticipated, most tumors were gastroenteropancreatic (GEP). Survival analyses demonstrated that non-GEP or stage IV tumors presented significantly lower overall survival (OS). Similarly, patients with surgery classified as R0 had better OS compared to R1, R2, or no surgery. Furthermore, patients with elevated chromogranin A (CgA) or high Ki67 showed a trend to poorer OS; however, these differences did not reach statistical significance (log-rank test p = 0.07). To the best of our knowledge, this is the first report of a NET registry in Chile. Median OS in our registry (110 months) is in line with other registries from Argentina and Spain. Other variables including age at diagnosis and gender were similar to previous studies; however, our data indicate a high proportion of small-bowel NETs compared to other cohorts, reflecting the need for NET regional registries. Indeed, these registries may explain regional discrepancies in incidence and distribution, adding to our knowledge on this seemingly rare, highly heterogeneous disease.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"3-10"},"PeriodicalIF":3.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0354-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36707712","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":"A Targeted Bivalent Androgen Receptor Binding Compound for Prostate Cancer Therapy.","authors":"Shafinaz Chowdhury,&nbsp;Lenore K Beitel,&nbsp;Rose Lumbroso,&nbsp;Enrico O Purisima,&nbsp;Miltiadis Paliouras,&nbsp;Mark Trifiro","doi":"10.1007/s12672-018-0353-6","DOIUrl":"https://doi.org/10.1007/s12672-018-0353-6","url":null,"abstract":"<p><p>The androgen-directed treatment of prostate cancer (PCa) is fraught with the recurrent profile of failed treatment due to drug resistance and must be addressed if we are to provide an effective therapeutic option. The most singular difficulty in the treatment of PCa is the failure to respond to classical androgen withdrawal or androgen blockade therapy, which often develops as the malignancy incurs genetic alterations and gain-of-function somatic mutations in the androgen receptor (AR). Physical cellular damaging therapeutic agents, such as radiation or activatable heat-generating transducers would circumvent classical \"anti-functional\" biological resistance, but to become ultimately effective would require directed application modalities. To this end, we have developed a novel AR-directed therapeutic agent by creating bivalent androgen hormone-AF-2 compounds that bind with high affinity to AR within cells. Here, we used molecular modeling and synthetic chemistry to create a number of compounds by conjugating 5α-dihydrotestosterone (DHT) to various AF-2 motif sequence peptides, through the use of a glycine and other spacer linkers. Our data indicates these compounds will bind to the AR in vitro and that altering the AF-2 peptide composition of the compound does indeed improve affinity for the AR. We also show that many of these bivalent compounds can readily pass through the plasma membrane and effectively compete against androgens alone.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 1","pages":"24-35"},"PeriodicalIF":3.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0353-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9901268","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":"Providing Evidence: Step by Step-a Letter from Associate Editor, Tobias Else, MD.","authors":"Tobias Else","doi":"10.1007/s12672-018-0355-4","DOIUrl":"https://doi.org/10.1007/s12672-018-0355-4","url":null,"abstract":"<p><p></p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"10 1","pages":"1-2"},"PeriodicalIF":3.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0355-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205106","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":"Diagnostic Performance of F-18 Fluorocholine PET/CT for Parathyroid Localization in Hyperparathyroidism: a Systematic Review and Meta-Analysis.","authors":"Seong-Jang Kim,&nbsp;Sang-Woo Lee,&nbsp;Shin Young Jeong,&nbsp;Kyoungjune Pak,&nbsp;Keunyoung Kim","doi":"10.1007/s12672-018-0347-4","DOIUrl":"https://doi.org/10.1007/s12672-018-0347-4","url":null,"abstract":"<p><p>The purpose of the current study was to investigate the diagnostic performance of F-18 Fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) for localization of hyperfunctioning parathyroid gland in patients with hyperparathyroidism (HPT) through a systematic review and meta-analysis. The MEDLINE/PubMed and EMBASE database, from the earliest available date of indexing through April 30, 2018, were searched for studies evaluating the diagnostic performance of F-18 FCH PET/CT for localization of hyperfunctioning parathyroid gland in patients with HPT. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves. Across eight studies (272 patients), the pooled sensitivity for F-18 FCH PET/CT was 0.90 (95% CI, 0.86-0.94) without heterogeneity (I² = 7.1) and a pooled specificity of 0.94 (95% CI, 0.90-0.96) with heterogeneity (I² = 79.8). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 5.3 (95% CI, 1.2-24.3) and negative likelihood ratio (LR-) of 0.15 (95% CI, 0.08-0.29). The pooled diagnostic odds ratio (DOR) was 38 (95% CI, 8-174). Hierarchical summary receiver operating characteristic (ROC) curve indicates that the areas under the curve were 0.9492 (SE, 0.0215). In meta-regression analysis, no definite variable was the source of the study heterogeneity. The current meta-analysis showed the high sensitivity and specificity of F-18 FCH PET/CT for localization of hyperfunctioning parathyroid gland. At present, the literature regarding the use of F-18 FCH PET/CT for localization of hyperfunctioning parathyroid gland remains still limited; thus, further large multicenter studies would be necessary to substantiate the diagnostic accuracy of F-18 FCH PET/for localization of hyperfunctioning parathyroid gland in patients with HPT.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 6","pages":"440-447"},"PeriodicalIF":3.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0347-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223752","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":"Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation.","authors":"Tung-Cheng Chang,&nbsp;Yu-Tang Chin,&nbsp;André Wendindondé Nana,&nbsp;Shwu-Huey Wang,&nbsp;Yu-Min Liao,&nbsp;Yi-Ru Chen,&nbsp;Ya-Jung Shih,&nbsp;Chun A Changou,&nbsp;Yu-Chen Sh Yang,&nbsp;Kuan Wang,&nbsp;Jacqueline Whang-Peng,&nbsp;Liang-Shun Wang,&nbsp;Steven C Stain,&nbsp;Ai Shih,&nbsp;Hung-Yun Lin,&nbsp;Chih-Hsiung Wu,&nbsp;Paul J Davis","doi":"10.1007/s12672-018-0341-x","DOIUrl":"https://doi.org/10.1007/s12672-018-0341-x","url":null,"abstract":"<p><p>Drug resistance complicates the clinical use of gefitinib. Tetraiodothyroacetic acid (tetrac) and nano-diamino-tetrac (NDAT) have been shown in vitro and in xenografts to have antiproliferative/angiogenic properties and to potentiate antiproliferative activity of other anticancer agents. In the current study, we investigated the effects of NDAT on the anticancer activities of gefitinib in human colorectal cancer cells. β-Galactoside α-2,6-sialyltransferase 1 (ST6Gal1) catalyzes EGFR sialylation that is associated with gefitinib resistance in colorectal cancers, and this was also investigated. Gefitinib inhibited cell proliferation of HT-29 cells (K-ras wild-type), and NDAT significantly enhanced the antiproliferative action of gefitinib. Gefitinib inhibited cell proliferation of HCT116 cells (K-ras mutant) only in high concentration, and this was further enhanced by NDAT. NDAT enhancedd gefitinib-induced antiproliferation in gefitinib-resistant colorectal cancer cells by inhibiting ST6Gal1 activity and PI3K activation. Furthermore, NDAT enhanced gefitinib-induced anticancer activity additively in colorectal cancer HCT116 cell xenograft-bearing nude mice. Results suggest that NDAT may have an application with gefitinib as combination colorectal cancer therapy.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"420-432"},"PeriodicalIF":3.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0341-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36464551","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":"Neck Ultrasound in Patients with Follicular Thyroid Carcinoma.","authors":"Konstantinos Segkos,&nbsp;Kyle Porter,&nbsp;Leigha Senter,&nbsp;Matthew D Ringel,&nbsp;Fadi A Nabhan","doi":"10.1007/s12672-018-0345-6","DOIUrl":"https://doi.org/10.1007/s12672-018-0345-6","url":null,"abstract":"<p><p>There are limited data on the role of neck ultrasound (US) in the surveillance of patients with follicular thyroid cancer (FTC). Here, we analyze the likelihood of US to find structural disease in patients with FTC and evaluate if initial American Thyroid Association (ATA) risk stratification and the response to therapy categories [the latter based on thyroglobulin (Tg) levels] modify that likelihood. We conducted a retrospective cohort study of 32 patients with FTC in our institution. We included all patients with well-differentiated FTC who underwent total thyroidectomy and radioactive iodine (RAI) treatment without neck structural disease at the time of RAI and with Tg and US at least 6 months after RAI. After a median follow-up of 4.3 years, two patients (6.3%) had structural disease by US. None of the 18 patients with initial ATA low-risk disease had structural disease by US in contrast to higher, but not significant, frequency of 18.2% (2/11) in patients with initial ATA high-risk disease (p = 0.14). Based on Tg levels, 24/32 patients had excellent response to therapy and 8/32 had biochemical incomplete/indeterminate response. None of the patients with excellent response had structural disease by US versus 2/8 (25%) patients with biochemical incomplete/indeterminate response all of whom had other sites of structural disease (p = 0.054). Our findings suggest that neck US in FTC is unlikely to find structural disease with initial low-risk ATA or excellent response to therapy but can detect structural disease in some patients with initial ATA high-risk or incomplete/indeterminate responses to therapy.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":" ","pages":"433-439"},"PeriodicalIF":3.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0345-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36380720","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 Importance of CYP19A1 in Estrogen Receptor-Positive Cholangiocarcinoma.","authors":"Waleeporn Kaewlert,&nbsp;Chadamas Sakonsinsiri,&nbsp;Nisana Namwat,&nbsp;Kanlayanee Sawanyawisuth,&nbsp;Piti Ungarreevittaya,&nbsp;Narong Khuntikeo,&nbsp;Napat Armartmuntree,&nbsp;Raynoo Thanan","doi":"10.1007/s12672-018-0349-2","DOIUrl":"https://doi.org/10.1007/s12672-018-0349-2","url":null,"abstract":"<p><p>CYP19A1, also called aromatase, is a key enzyme for converting androgens to estrogens of estrogen synthesis. Elevated serum estrogen and high expression levels of estrogen-related proteins are found in cholangiocarcinoma (CCA; bile duct cancer). However, the expression of CYP19A1 in relation to estrogen-related proteins, including estrogen receptors (ERα, ERβ, and GPR30) and an estrogen response protein (TFF1), has never been explored in CCA. In this study, we investigated the expressions of CYP19A1 and estrogen-related proteins in CCA tissues (n = 74; 51 males and 23 females) using immunohistochemistry. The results showed that CYP19A1 was overexpressed in CCA cells compared with that in normal bile duct cells in the adjacent tissues. High expression of CYP19A1 was correlated with the metastatic status of the patients. High CYP19A1 expression was also positively correlated with GPR30 expression. Correlation between high CYP19A1 expression in the tumor tissues and shorter survival time was more prominent in male than in female CCA patients. To elucidate further, the effect of CYP19A1 knockdown on a CCA cell line was examined using a specific siRNA. When CYP19A1 gene expression was suppressed, migration and proliferation activities of CCA cells were significantly reduced. Moreover, the cell proliferation of high CYP19A1-expressing KKU-213 cells was more profoundly suppressed by CYP19A1 inhibitors (exemestane and letrozole) than low CYP19A1-expressing KKU-100 cells. Thus, CYP19A1 promotes CCA progression with aggressive clinical outcomes via increased migration and proliferation activities of cancer cells. CYP19A1 can be a potential chemotherapeutic target for CCA, especially in male patients.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 6","pages":"408-419"},"PeriodicalIF":3.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0349-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205099","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 Evolution of Estrogen Receptor Signaling in the Progression of Endometriosis to Endometriosis-Associated Ovarian Cancer.","authors":"Courtney L Andersen,&nbsp;Michelle M Boisen,&nbsp;Matthew J Sikora,&nbsp;Tianzhou Ma,&nbsp;George Tseng,&nbsp;Swati Suryawanshi,&nbsp;Anda Vlad,&nbsp;Esther Elishaev,&nbsp;Robert P Edwards,&nbsp;Steffi Oesterreich","doi":"10.1007/s12672-018-0350-9","DOIUrl":"https://doi.org/10.1007/s12672-018-0350-9","url":null,"abstract":"<p><p>To investigate changes in estrogen receptor alpha (ERα) signaling during progression of endometriosis to endometriosis-associated ovarian cancer (EAOC) as a driver of malignant transformation. We procured tissue samples of normal endometrium, endometriosis (benign, atypical, concurrent with EAOC), and EAOC. We evaluated expression of a 236-gene signature of estrogen signaling. ANOVA and unsupervised clustering were used to identify gene expression profiles across disease states. These profiles were compared to profiles of estrogen regulation in cancer models from the Gene Expression Omnibus (GEO). Gene Set Enrichment Analysis (GSEA) was performed to determine whether gene expression in EAOC was consistent with ERα activity. ANOVA revealed 158 differentially expressed genes (q < 0.05) and unsupervised clustering identified five distinct gene clusters. The estrogen signaling profile of EAOC was not consistent with activated ERα in pre-clinical models. Gene set enrichment analysis did not identify signatures of activated ERα in EAOC but instead identified expression patterns consistent with loss of ERα function and development of endocrine resistance. Gene expression data suggest that ERα signaling becomes inactivated throughout the progression of endometriosis to EAOC. The gene expression pattern in EAOC is more consistent with profiles of endocrine resistance.</p>","PeriodicalId":13060,"journal":{"name":"Hormones & Cancer","volume":"9 6","pages":"399-407"},"PeriodicalIF":3.0,"publicationDate":"2018-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12672-018-0350-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205105","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}