Differential expression of C-CAM cell adhesion molecule in prostate carcinogenesis in a transgenic mouse model.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
C-CAM expression correlates with the differentiation states of prostate epithelia and is down regulated early in prostate tumorigenesis in the TRAMP model.
Pu
Y S
YS
Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Luo
W
W
Lu
H H
HH
Greenberg
N M
NM
Lin
S H
SH
Gingrich
J R
JR
D000251:Adenosine Triphosphatases / Q000096:biosynthesis* / Q000235:genetics*; D000818:Animals; D015703:Antigens, CD; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006023:Glycoproteins; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*
D015703:Antigens, CD; C069847:CD66 antigens; C087701:Ceacam2 protein, mouse; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D000251:Adenosine Triphosphatases