Roles of estrogen receptors and estrogen-responsive genes in the development of benign prostatic hyperplasia and prostate cancer

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We investigated expression of ERα, wild-type ERβ(wtERβ) and a C-terminal truncated splice variant of ERβ(ER,βex) in 50 benign and 100 malignant human prostatic tissue samples by immunohistochemistry. While strong immunostaining of ERα was consistently identitied in stioinal cmpartment, wtERβ was expressed in epithelial cells in both the benign and malignant foci. However, wtERβ expression was significantly lower in the cancers than in the benign epithellum, and inversely correlated with Gleason tumor gradle (p<0.0001 and p=0.0099, respectively). In contrast, ERβcx was significantly more expressed in the high grade cancers(83%), compared with the low grade tumors (22%) and the benign sites (11%)(p<0.0001,both). Cancer-specific survival of patients with lower wtERβ expression was significantly worse than those with higher expression of wtERβ(p=0.0018). Conversely, higher ER β expression significantly correlated with poor cancer-specific survival(p=0.0058). These results suggest that diff … More erential expression of wtERβ and ERI8 ex may be prognostic predictorss for prostatic cancer.Estrogen Receptor-binding Fragmentassocoiated Gene 9 (EBAG 9) has been identified as a primary estrogen-responsive gene from MCF-7 human breast cancer cells (Watanabe T, et al., Mol Cell Biol,1998; 18: 442-449). EBAGO is identical with RCAS1(Receptor-inding cancer antigen expressed on SiSo cells), Which has been reported as a cancer cell surface antigen implicated in immune escape (Nithashima M, et al., Nat Med, 1999; 5 938-942). In the present study, we examined EBAG9 expression in human prostatic tissues, and investigated its prognostic significance in patients with prostatic cancer. EBAG9 expression in normal prostatic epithelial cells and PC-3, DU145, LNCaP cancer cells was determined by Western blot analysis. Immunohistochemical analysis was performed in 21 benign and 81 malignant prostatic spocimens, and patients' charts were reviewed for clinical, pathological, and survival data. EBAG9 was abundantly expressed in the prostate cancer cells, compared with the normal epithelird cells. Strong mmdl (liffuse immunostaining in the cytoplasmn of EBAG9 was found in 44 of 81(54%) cancerous tissue samples, EBAG9 expression significantly correlated with advancedl 1)flthological stages and high Gleason score (p=0.030 and l < 0.0001, respectively). EBAG9 was more frequently expressed at sites of capsular penetration (79%) audI lymnph nodle metastasis (100%), coml)ared with intracapsular primary tumors (54%) (p0.02G4 and 0.0018, respectively). Positive EBAG9 immnunoreactivity significantly correlated with poor PSA failurefree survival (p=0.0059). EBAG9/RCAS1 may play a significant role in the cancer rogression via an immune escape system. Immunodletection of EBAG9/RCAS1 expression can be a negative progflostic indlicator for patients with prostatic cancer. Less