Down regulation of adhesion protein E-cadherin in Epstein-Barr virus infected nasopharyngeal carcinomas.
Nasopharyngeal carcinoma (NPC) is a unique tumour due to its aetiology, incidence pattern and its consistent association with Epstein-Barr virus (EBV). EBV encodes many viral proteins, which targets crucial cell cycle regulatory proteins. Cadherins are a family of transmembrane glycoproteins, which mediates Ca2+-dependent intercellular adhesion. Epithelial (E)-cadherin is an important member of this family, which is expressed predominantly on the surface of epithelial cells. E-cadherin acts as an invasion/metastasis-suppressor gene, hence knowledge of the molecular mechanism that controls its expression or function is of primary importance in understanding the process of tumor invasion. Loss of E-cadherin function has been shown to potentiate tumor cell invasion and interestingly, a large number of invasive tumors do not involve mutation of E-cadherin, but rather down regulation of expression. Hence in this study, an attempt was made to evaluate the protein level expression pattern of E-cadherin in relation to viral involvement and to correlate it with other clinico-pathological parameters. We observed a significant down regulation of E-cadherin in NPC and its histological subsets, when compared to the controls (p<0.001). Expression of E-cadherin ranged from mild to moderate and none of the NPC showed intense expression. E-cadherin expression showed a significant down-regulation in NPC lesions with EBV infection (r=-0.436, p<0.001). The down regulation of E-cadherin observed in NPC is in line with the previous reports in E-cadherin expression in various cancers. The total lack of E-cadherin expression in neoplastic cells might be due to hypermethylation of E-cadherin promoter or its down regulation by cellular transcription repressor. Our study also shows a significant down regulation of E-cadherin in the presence of EBV, which also might involve the cellular DNA methylation machinery.
Krishna
Smriti M
SM
Division of Cancer Research, Regional Cancer Centre, Medical College. P.O, Trivandrum- 695 011, Kerala, India. smritimk@hotmail.com
Kattoor
Jayashree
J
Balaram
Prabha
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015536:Down-Regulation; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000821:virology
D015820:Cadherins; D015815:Cell Adhesion Molecules