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.

Down-regulation of μ-protocadherin expression is a common event in colorectal carcinogenesis / Losi, Lorena; Parenti, Sandra; Fabrizio, Ferrarini; Rivasi, Francesco; Margherita, Gavioli; Gianni, Natalini; Ferrari, Sergio; Grande, Alexis. - In: HUMAN PATHOLOGY. - ISSN 0046-8177. - STAMPA. - 42:(2011), pp. 960-971. [10.1016/j.humpath.2010.10.009]

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

LOSI, Lorena;PARENTI, Sandra;RIVASI, Francesco;FERRARI, Sergio;GRANDE, Alexis
2011-01-01

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.
42
960
971
Down-regulation of μ-protocadherin expression is a common event in colorectal carcinogenesis / Losi, Lorena; Parenti, Sandra; Fabrizio, Ferrarini; Rivasi, Francesco; Margherita, Gavioli; Gianni, Natalini; Ferrari, Sergio; Grande, Alexis. - In: HUMAN PATHOLOGY. - ISSN 0046-8177. - STAMPA. - 42:(2011), pp. 960-971. [10.1016/j.humpath.2010.10.009]
Losi, Lorena; Parenti, Sandra; Fabrizio, Ferrarini; Rivasi, Francesco; Margherita, Gavioli; Gianni, Natalini; Ferrari, Sergio; Grande, Alexis
File in questo prodotto:
File Dimensione Formato  
Human Pathology 2011. Losi.pdf

non disponibili

Tipologia: Versione dell'autore revisionata e accettata per la pubblicazione
Dimensione 3.38 MB
Formato Adobe PDF
3.38 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/703925
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 16
  • ???jsp.display-item.citation.isi??? 16
social impact