In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the context of a neo-adjuvant chemotherapy trial.
However, association analyses of two polymorphisms suggest that the ER-alpha gene or a gene located close to the ER-alpha locus might be related to susceptibility of familial ovarian cancer without BRCA1 mutation.
These results indicate that aberrant hypermethylation may be responsible for a significant proportion of epithelial ovarian tumours in which oestrogen receptor alpha expression is lost.
In addition, intracellular hK4 levels, as detected on Western blot analysis, were induced by 100 nM estrogen treatment of the estrogen receptor positive ovarian carcinoma cell line OVCAR-3, >8-24 h. Our results show that the level of KLK4 expression and expression of KLK4 mRNA variants are associated with progression of ovarian cancer, particularly late stage SER adenocarcinomas.
The identification of a second estrogen receptor gene (ERbeta), expressed predominantly in ovarian granulosa cells, led us to explore its possible role in ovarian cancer, particularly in granulosa cell tumors (GCT).
Conversely, estrogen did not influence expression of BRCA1 in HBL-100 cells that lacked the estrogen receptor, although the constitutive levels of BRCA1 mRNA (but not protein) in these cells were 5- to 30-fold higher than in other breast and ovarian cancer cells.
All these data are consistent with E2 increasing production of TGFalpha in ER-positive ovarian cancer and this in turn acting through the EGF receptor to modulate growth in an autocrine manner.
Additionally, we found elevated binding of the estrogen receptor (ER) in H-ras ER element in all pairs of ovarian tumor/normal tissue tested, whereas in ER-negative control breast tumor/normal tissue pairs, no differences in ER DNA-binding levels were observed.