Steroidogenesis in steroid related cancers

[摘要] Prostate cancer growth is androgen dependent, but can bypass treatments inhibiting androgen production and continues to grow, probably utilising the adrenal alternative dihydrotestosterone (DHT) biosynthesis pathway. In contrast, the role of steroids in ovarian cancer is not clearly defined, although it is known that progesterone and oestrogens affect this cancer proliferation. The thesis aims were to investigate steroid relation with prostate and ovarian cancers as well as characterise three adrenocortical carcinoma cell (ACC) lines derived from H295 cell line. The steroidogenesis characterisation of three ACC cell line strains indicated that they have similar steroidogenic capability to the native adrenal cortex. Another ACC cell line, H295R1, was used to investigate whether CYP17A1, a key enzyme in androgen synthesis, inhibition was sufficient to cause a shift towards the alternative DHT biosynthesis pathway. Although knockdown was achieved and affected steroidogenesis, no shift towards the alternative pathway was demonstrated. The ovarian cancer cell lines, A2780, COV434, CaOv-3 and OAW42, showed steroidogenic capabilities suggesting that the tumours are probably transformed with steroidogenic capability. The results obtained indicate that the adrenal gland might have a role in prostate cancer resistance to treatment. They also demonstrate that ovarian cancer might be steroid-producing and/or dependent.

[发布机构] University:University of Birmingham;Department:Institute of Metabolism and Systems Research

[关键词] R Medicine;RC Internal medicine;RC0254 Neoplasms. Tumors. Oncology (including Cancer)