DIFFERENTIAL EXPRESSION OF C-CAM CELL ADHESION MOLECULE IN PROSTATE CARCINOGENESIS IN A TRANSGENIC MOUSE MODEL

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Abstract
The transgenic adenocarcinoma of mouse prostate (TRAMP) model, in which various grades of prostate intraepithelial neoplasia (PIN) and prostate cancer with metastases can be reproducibly generated, is a paradigm for prostate disease progression. We have previously shown that C-CAM, an adhesion molecule, can suppress the growth of prostate cancer. In this report, we describe immunohistochemical characterization of differential expression of C-CAM at various stages of prostate tumorigenesis in the TRAMP model. We sampled prostate specimens and periaortic lymph nodes from TRAMP mice. Indirect immunohistochemical staining with a polyclonal anti-C-CAM antibody was performed on the formalin-fixed, paraffin-embedded specimens. After castration at 12 weeks of age, the TRAMP mice developed androgen-independent prostate cancer (AIPC) and lymph node metastasis at 18 to 24 weeks of age. Samples from these castrated mice were also analyzed. C-CAM protein was expressed in the normal prostate epithelia of non-transgenic and TRAMP mice as well as in low-grade PINs in TRAMP mice. Expression was uniform on the luminal surfaces of these epithelia. C-CAM expression was noticeably reduced and the staining pattern heterogeneous in some high-grade PINs. C-CAM staining was generally absent in prostate cancer and metastatic lymph nodes. Androgen independent prostate cancer and its metastatic tumors generated in castrated TRAMP mice were also C-CAM negative. C-CAM expression correlates with the differentiation states of prostate epithelia and is down regulated early in prostate tumorigenesis in the TRAMP model.

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