Androgens stimulate telomerase expression, activity and phosphorylation in ovarian adenocarcinoma cells
ABSTRACT Androgens have been implicated in increasing ovarian cancer risk. Most ovarian cancer cells have high telomerase activity which is effective in inducing ovarian carcinogenesis. The purpose of this study was to investigate the effects of testosterone and androstenedione on the viability of an ovarian adenocarcinoma cell line, the activity and expression of telomerase, and the phosphorylation status of its catalytic subunit in these cells. Results showed that androgens significantly increased the viability of ovarian cancer cells and that these hormones induced the expression, activity and phosphorylation of telomerase. This upregulation was blocked by phosphatidylinositol 3-kinase pathway inhibitors. These findings might have implications for understanding the role of androgens in ovarian carcinogenesis.
- SourceAvailable from: Kwong-Kwok Wong
- "Shi et al. (2011) examined the role of DHT, testosterone, and dehydroepiandrosterone (DHEA) in breast and ovarian cancer cell lines, and found that DHT but not the other androgens induced the degradation of the tumor suppressor p27 in both cell lines. Furthermore, in ovarian carcinoma cell lines, testosterone and androstenedione were found to increase cell viability, and induce telomerase activity which was blocked by PI3K inhibitors (Nourbakhsh et al., 2010). Sheach et al. (2009) found that the ovarian cancer cell lines OVCAR3 and OSEC2 expressed the androgen receptor, and treatment with androgen upregulated 121 genes, including G-protein-related genes Rab25 and Rab35. "
Chapter: Steroid Hormones and Ovarian CancerSteroids - Clinical Aspect, 10/2011; , ISBN: 978-953-307-705-5
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ABSTRACT: TMPRSS2:ERG is a gene fusion resulting from the chromosomal rearrangement of the androgen-regulated TMPRSS2 gene and the ETS transcription factor ERG, leading to the over-expression of the oncogenic molecule ERG. This gene rearrangement has been found in approximately half of all prostate cancers and ERG overexpression is considered as a novel diagnostic marker for prostate carcinoma. However, little is known about the role of the TMPRSS2:ERG gene fusion in ovarian cancer. The purpose of this study was to test ERG expression in ovarian cancer and its potential as a diagnostic marker for ovarian carcinoma progression. A tissue microarray containing 180 ovarian cancer tissues of various pathological types and grades were examined by immunohistochemical analysis for expression of ERG. We also used 40 prostate carcinoma tissues and 40 normal tissues for comparison in parallel experiments. ERG-positive expression was detected in 40% of the prostate tumor cancer, as well as in internal positive control endothelial cells, confirming over-expression of ERG in prostate cancer at relatively the same rate observed by others. In contrast, all of the ovarian tumor patient tissues of varying histologic types were ERG-negative, despite some positivity in endothelial cells. These results suggest that the oncogenic gene fusion TMPRSS2:ERG does not occur in ovarian cancer relative to prostate cancer. Therefore, development of ERG expression profile would not be a useful diagnostic or prognostic marker for ovarian cancer patient screening.International journal of clinical and experimental pathology 01/2011; 4(7):644-50. · 1.78 Impact Factor
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ABSTRACT: Androgen receptors are frequently expressed in epithelial ovarian cancer (EOC). Their role in the development of EOC is not fully understood. In the present review we first discuss the epidemiological data linking a hyperandrogen state to a higher risk for ovarian cancer, second describe in vitro studies of the role of androgens in influencing the growth of EOC, and finally review the completed clinical trials with compounds that exploit the androgen axis in patients with ovarian cancer. The therapeutic approaches that inhibit androgen signaling have so far produced only modest response rates. In the light of new data regarding the role of androgen stimulation in the evolution of EOC and the emergence of new compounds used for the treatment of other hormone-driven malignancies, such as prostate and breast cancer, we provide suggestions for new studies of antiandrogen therapeutics in the treatment of EOC. A specific example is the new agent abiraterone. In addition, we propose a panel of molecules that could be assessed as potential biomarkers that may aid patient selection for this approach in the future.The Oncologist 09/2011; 16(10):1413-21. DOI:10.1634/theoncologist.2011-0164 · 4.54 Impact Factor