Molekulare und genetische Medizin

Estrogen Receptor Subtype Expression is Altered in the Hen Model of Ovarian Cancer

Abstract

Lindsey S. Treviño and Patricia A. Johnson

There is growing evidence that estrogens may promote tumor progression, including ovarian tumors. Estrogens exert their actions in tissues through two different receptor subtypes (ESR1 and ESR2). Studies have shown that hens develop ovarian cancer spontaneously, therefore providing a suitable animal model for the disease. Our aim was to determine the expression of mRNA and protein of the estrogen receptor subtypes in ovaries of normal hens and ovaries from hens with ovarian cancer. Ovarian tissue from normal hens and hens with ovarian cancer was collected for quantitative real-time PCR and immunofluorescence analysis. Quantitative real-time PCR results showed that the relative mRNA expression of ESR1 and the ratio of ESR1/ESR2 are significantly greater from hens with ovarian cancer when compared to normal ovarian tissue. Immunofluorescence analysis showed differential ESR1 and ESR2 protein expression in ovarian tissue sections from normal hens and hens with ovarian cancer, with results parallel to the mRNA data. There was no significant difference in plasma estradiol levels between normal hens and hens with ovarian cancer. These data suggest an increase in downstream estrogen-mediated actions in chicken ovarian tumors and, indeed, microarray analysis reveals a functionally significant estradiol-signaling pathway in chicken ovarian tumors. Interestingly, expression of a putative ovarian tumor suppressor, EPB41L3, is down regulated in this pathway. Taken together, these results suggest that, in the hen, ESR1 may be mediating a proliferative response in ovarian cancer cells. Although additional studies are required to define the role of ESR1 in tumor formation in the hen, these results support the utility of the hen for testing possible endocrine therapies.