title: Down-regulation of μ-protocadherin expression is a common event in colorectal carcinogenesis.
abstract: 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 μ-protocadherin, which is able to sequester β-catenin on plasmatic membrane of treated cells inhibiting its proliferation signalling pathway. This finding suggests that μ-protocadherin could exert an oncosuppressive effect on colorectal epithelium. The purpose of our study was to assess whether μ-protocadherin expression is down-regulated during colorectal carcinogenesis. This issue was addressed by analyzing the messenger RNA and protein expression of μ-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 μ-protocadherin in the pathogenesis of colorectal cancer, this last assay was also extended to β-catenin, E-cadherin, and Ki-67 proteins. The results obtained evidenced that (1) levels of μ-protocadherin transcript were down-regulated in all the analyzed colorectal cancer samples as compared with normal mucosa; (2) expression of μ-protocadherin protein was completely lost in most analyzed colorectal cancer samples (71%); (3) μ-protocadherin retains β-catenin on the plasmatic membrane of normal colon enterocytes, which implies that β-catenin is released from this site and translocated to the nucleus in colorectal cancer cells. Our data consequently suggest that down-regulation of μ-protocadherin expression is a common event in colorectal carcinogenesis and might therefore play an important role in this pathologic process.
authors.affiliation: Department of Pathological Anatomy, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Losi
authors.forename: Sandra
authors.initials: S
authors.lastname: Parenti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ferrarini
authors.forename: Francesco
authors.initials: F
authors.lastname: Rivasi
authors.forename: Margherita
authors.initials: M
authors.lastname: Gavioli
authors.forename: Gianni
authors.initials: G
authors.lastname: Natalini
authors.forename: Sergio
authors.initials: S
authors.lastname: Ferrari
authors.forename: Alexis
authors.initials: A
authors.lastname: Grande
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C413024:CDHR5 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D012333:RNA, Messenger; D051176:beta Catenin