ER and PR in renomedullary interstitial cells during Syrian hamster estrogen-induced tumorigenesis: Evidence for receptor-mediated oncogenesis

The estrogen-induced and -dependent Syrian hamster renal tumor is the most intensively studied model in estrogen carcinogenesis. Yet, it remains confo unding that the kidney of this species behaves as an estrogen target tissue . As both reproductive and urinary systems arise from the same germinal rid ge, we propose that some of the germinal cells, normally destined for the u terus, migrate and establish themselves in the renal corticomedullary regio n in this hamster strain. These ectopically located germinal cells remain d ormant unless exposed to estrogen. Supporting this contention, a subset of renal interstitial cells, primarily located in the corticomedullary region, express PR after only 2 wk and ER alpha after 1.5-3.0 months of estrogen t reatment. As treatment continues, groups of cells of the renal interstitium . and small and large renal tumors show ER alpha (+) and PR+ staining. Alth ough ER alpha and PR isoform profiles in estrogen-treated hamster kidneys a re distinctly different from corresponding uterine patterns, both receptor isoform profiles in primary renal tumors closely resemble those seen in ham ster uteri. Renal ER alpha protein and mRNA expression increased after 2.0 and 4.0 months of estrogen treatment and in all renal tumors examined. Usin g nuclear image cytometry, both early small and large renal tumors were hig hly aneuploid, indicating that genomic instability is probably a critical e arly event in estrogen carcinogenesis.