ER and PR in Renomedullary Interstitial Cells During Syrian Hamster Estrogen-Induced Tumorigenesis: Evidence for Receptor-Mediated Oncogenesis

Abstract

The estrogen-induced and -dependent Syrian hamster renal tumor is the most intensively studied model in estrogen carcinogenesis. Yet, it remains confounding that the kidney of this species behaves as an estrogen target tissue. As both reproductive and urinary systems arise from the same germinal ridge, we propose that some of the germinal cells, normally destined for the uterus, migrate and establish themselves in the renal corticomedullary region in this hamster strain. These ectopically located germinal cells remain dormant 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 treatment. As treatment continues, groups of cells of the renal interstitium and small and large renal tumors show ER alpha(+) and PR(+) staining. Although ER alpha and PR isoform profiles in estrogen-treated hamster kidneys are distinctly different from corresponding uterine patterns, both receptor isoform profiles in primary renal tumors closely resemble those seen in hamster 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. Using nuclear image cytometry, both early small and large renal tumors were highly aneuploid, indicating that genomic instability is probably a critical early event in estrogen carcinogenesis.

Toward functional glycomics by localization of tissue lectins: immunohistochemical galectin fingerprinting during diethylstilbestrol-induced kidney tumorigenesis in male Syrian hamster

“…The estrogen-induced tumor in male SHK represents a unique model for the study of estrogen-dependent renal malignancies Li 1984, 1990;Liehr et al 1986;Liehr 1997Liehr , 2001Li et al 2001). There is a controversy about the cell of origin and the processes involved in this model during tumorigenesis (Hacker et al 1988).…”

“…There is a controversy about the cell of origin and the processes involved in this model during tumorigenesis (Hacker et al 1988). Different studies, as outlined in the Introduction, have suggested that the cells of origin might be interstitial stem cells mainly found at the corticomedullary junction (Oberley et al 1991), cells of the juxtaglomerular apparatus (Dodge et al 1988), vascular smooth muscle cells (Hacker et al 1988), or unidentified dormant germinal cells ectopically located in kidney (Li et al 2001). A recent immunohistochemical study raised the possibility that DES-induced SHKT could originate from a yet unidentified precursor cell located in the sheath of peripheral nerves (Toubeau et al 2001).…”

“…According to different studies, the estrogen-induced renal tumorigenesis in the hamster seems strictly dependent of estrogen exposure (Yager and Liehr 1996;Li et al 2001;Toubeau et al 2001). Moreover, the presence of estrogen receptors has been reported in Schwann cells growing in vitro (Jung-Testas et al 1994;Do Thi et al 1998) as well as in the HKT-1097 cell line derived from SHKT (Laurent et al 1999).…”

“…Later, Goldfarb and Pugh (1990) disclosed an important histological similarity between early neoplastic buds and DES-induced tubular dysplasia, and proposed to classify SHKT as carcinomas originating from proximal tubules. Recent immunohistochemical investigations have postulated other cells of origin such as smooth muscle cells (Hacker et al 1988), a subpopulation of mesenchymal stem cells (Gonzalez and Oberley 1989), juxtaglomerular cells (Dodge et al 1988), undifferentiated renal interstitial cells (Llombart-Bosch and Peydro 1975;Oberley et al 1991;Bhat et al 1993;Cortes-Vizcaino et al 1994), or dormant germinal cells ectopically located in the kidney (Li et al 2001). Our group reported the presence of a variety of neuroectodermal markers in SHKT cells both in vitro (Laurent et al 1999) and in vivo (Toubeau et al 2001;Nonclercq et al 2002).…”

Towards functional glycomics by localization of binding sites for tissue lectins: lectin histochemical reactivity for galectins during diethylstilbestrol-induced kidney tumorigenesis in male Syrian hamster

“…Estrogen-induced renal tumors in adult male Syrian hamster (SHKT) represent an extensively used animal model for the study of hormonal and renal carcinogenesis, which can potentially provide insights to understanding origin and progression of related human malignancies Li 1984, 1990;Li et al 2001;Liehr 1997Liehr , 2001Liehr et al 1986). Of note, immunohistochemical analysis of steroid hormone receptor expression in human renal cell carcinomas (RCC) has detected estrogen and progesterone receptors in a small number of cases (Di Silverio et al 1997;Brown et al 1998;Langner et al 2004).…”