Altered expression of androgen-receptor isoforms in human colon-cancer tissues.

Many groups have examined of androgen the effects on normal and neoplastic colon tissues, but no clear picture has hitherto emerged. In particular, the presence and the function of the androgen receptor (AR) has only partially been investigated in the past. The present study reports analysis of expression of the AR gene as messenger RNA and as protein in surgical samples of neoplastic colon mucosa and of corresponding healthy surrounding tissue. Specific binding for DHT, demonstrating the presence of AR, was observed in almost all the samples (2 samples out of 12 were negative). No significant difference was observed between healthy and neoplastic mucosa, or between male and female patients. A further characterization of AR was performed with Western blot, using 2 different primary antibodies. Both AR isoforms, AR-B and AR-A, were detected in healthy mucosa, while only AR-A, resolving at 87 kDa, was observed in neoplastic mucosa. RT-PCR analysis revealed the transcript for AR in both healthy and neoplastic mucosa in 10 samples; no message was detectable in 2 samples (negative also for binding); 2 additional samples presented AR mRNA only in healthy colon mucosa, 2 others only in neoplastic mucosa. In addition, a variant AR messenger RNA, probabily derived from alternative splicing, was observed. We found that AR is expressed both in healthy and in neoplastic colon mucosa, either as mRNA or as protein. Neoplastic colon tissue shows a characteristic loss of expression of the AR-B isoform, while AR-A expression is maintained. These findings underscore the possible role of androgen and its receptor in colon carcinogenesis. Copyright 2000 Wiley-Liss, Inc.