Expression and androgen regulation of C-CAM cell adhesion molecule isoforms in rat dorsal and ventral prostate.
C-CAM is an epithelial cell adhesion molecule with two major splice variants that differ in the length of the cytoplasmic domain. C-CAM1 (long (L)-form) strongly suppresses the tumorigenicity of human prostate carcinoma cells. In contrast, C-CAM2 (short (S)-form) does not exhibit tumor-suppressive activity. In the present study we have investigated the functional significance of L-form and S-form C-CAM in rat prostate by examining their expression and distribution in different prostate lobes and their response to androgen deprivation. RNase protection assays with a probe for both C-CAM isoforms detected high levels of C-CAM messages in the rat dorso-lateral prostate (DLP). L- and S-form proteins, localized by indirect immunofluorescence using isoform-specific antipeptide antibodies, were co-expressed on the apical surface of prostate epithelial cells in normal DLP. Androgen depletion did not significantly change the steady state levels of C-CAM message and protein expression in the DLP, although there was a change in the pattern of protein expression in these lobes. In contrast, C-CAM isoform messages and proteins were undetectable in normal ventral prostate (VP) but increased markedly in this lobe in response to castration, producing isoform ratios similar to those in DLP. These results demonstrate that coordinate expression of C-CAM isoforms is maintained in the VP following androgen depletion and suggest that androgen suppresses C-CAM expression in VP but not in DLP. These results suggest that balanced expression of L- and S-form C-CAM is important for normal prostate growth and differentiation.
Makarovskiy
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Department of Molecular Pathology, The University of Texas, MD Anderson Cancer Center, Houston 77030, USA.
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Earley
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Paglia
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Hixson
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D000251:Adenosine Triphosphatases / Q000096:biosynthesis* / Q000235:genetics; D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD; D002272:Carcinoembryonic Antigen; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D006023:Glycoproteins; D008297:Male; D051379:Mice; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
D000728:Androgens; D015703:Antigens, CD; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; C087701:Ceacam2 protein, mouse; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D020033:Protein Isoforms; D000251:Adenosine Triphosphatases