Down-regulation of mu-protocadherin expression is a common event in colorectal carcinogenesis

作者：Losi Lorena; Parenti Sandra; Ferrarini Fabrizio; Rivasi Francesco; Gavioli Margherita; Natalini Gianni; Ferrari Sergio; Grande Alexis^*

来源：Human Pathology, 2011, 42(7): 960-971.

DOI：10.1016/j.humpath.2010.10.009

• mu-Protocadherin
• beta-Catenin
• Cell adhesion molecules
• Colorectal cancer
• 5-ASA

We have previously reported that treatment of colorectal cancer cells with mesalazine results in the up-regulated expression of a novel member of the cadherin protein superfamily, named mu-protocadherin, which is able to sequester beta-catenin on plasmatic membrane of treated cells inhibiting its proliferation signalling pathway. This finding suggests that mu-protocadherin could exert an oncosuppressive effect on colorectal epithelium. The purpose of our study was to assess whether mu-protocadherin expression is down-regulated during colorectal carcinogenesis. This issue was addressed by analyzing the messenger RNA and protein expression of mu-protocadherin in normal and tumor colorectal cell samples using a combination of quantitative real-time polymerase chain reaction, microarray analysis, and immunohistochemical examination. To better contextualize the role played by mu-protocadherin in the pathogenesis of colorectal cancer, this last assay was also extended to beta-catenin, E-cadherin, and Ki-67 proteins. The results obtained evidenced that (1) levels of mu-protocadherin transcript were down-regulated in all the analyzed colorectal cancer samples as compared with normal mucosa; (2) expression of mu-protocadherin protein was completely lost in most analyzed colorectal cancer samples (71%); (3) mu-protocadherin retains beta-catenin on the plasmatic membrane of normal colon enterocytes, which implies that beta-catenin is released from this site and translocated to the nucleus in colorectal cancer cells. Our data consequently suggest that down-regulation of mu-protocadherin expression is a common event in colorectal carcinogenesis and might therefore play an important role in this pathologic process.

• 出版日期2011-7