Endocrine Abstracts

Ovarian cancer is the most fatal of all gynaecological malignancies. EOC accounts for >90% of malignant ovarian tumours and is thought to originate mostly from OSE cells. Epidemiological data suggest EOC is oestrogen responsive and we previously showed active oestrogen could be produced locally by EOC cells, but not by normal OSE cells, through the combined activities of steroid sulfatase (STS) and 17βhydroxysteroid dehydrogenase. We now investigate if EST, which converts oestrone (E₁) to oestrone sulphate (E₁S), might also affect the formation of active oestrogen in EOC cells relative to normal OSE cells.

SKOV-3, PEO-14, PEO-1 and PEO-4 ovarian cancer cell lines, primary EOC cells and normal human OSE cells were cultured for 48 h with/without the inflammatory cytokine interleukin-1α (IL-1α). Total RNA was extracted and analysed for expression of EST mRNA using quantitative RT-PCR. Radiometabolic analysis was used to determine EST and STS enzymic activities in cultured cell monolayers.

EST mRNA expression was much lower in primary EOC cells and all ovarian cancer cell lines than in normal OSE cells, suggesting that the lower expression of EST in cancer could favour the active oestrogen production. Furthermore, we found normal OSE cells and PEO-14 cells responded to IL-1α with 81.24 and 92.8% inhibition respectively in EST mRNA expression (P<0.05). Additionally, in normal OSE cells there is lower conversion rate of ³H-E₁S to ³H-E but higher rate of ³H-E₁ to ³H-E₁S, indicating EST is more active than STS in normal OSE cells. This situation was reversed in SKOV-3 cells.

These results indicate that ovarian cancer cells contain the machinery for producing active oestrogen from inactive conjugated oestrogens. Moreover STS (which actives oestrogen) is increased by IL-1α while EST (which inactive oestrogen) is inhibited by IL-1α. Thus we demonstrate a potential mechanism for inflammation-associated, oestrogen-mediated enhancement of ovarian tumour development.