Altered transcription and expression of PTEN in breast tumors: is it regulated by hypermethylation?

Breast cancer (BC) is the commonest cancer in women worldwide with a widely variable incidence between countries and regions. BC is either familial or sporadic. Mutations in tumor suppressor gene, PTEN has been associated with syndromic BC and in a subset of sporadic BCs. The present study was carried out in archival formalin fixed paraffin embedded samples. Immunohistochemistry and quantitative RTPCR indicated a reduced expression/ transcription of PTEN in tumor as compared to adjacent non-tumorous tissue. However, the promoter methylation evaluated by Methylation Specific Restriction Assay indicated that only 20% of the tumors showed PTEN methylation and could not account for the rest of the samples with reduced expression. Overall evidence from literature and our present findings indicate that: (i) Loss of Heterozygosity at PTEN gene locus (ii) germline and somatic gene mutations of PTEN (iii) epigenetic silencing by methylation in PTEN promoter CpG cluster (iv)protein interactions which reduce PTEN transcription and (v) PTEN protein degradation together play an important role in the etiology of BC.