Reactivation of epigenetically silenced HER4/ERBB4 results in apoptosis of breast tumor cells.

ABSTRACT: Experimental and clinical data support a growth inhibitory role for HER4 in breast cancer. Clinically HER4 expression is extinguished during breast tumorigenesis supporting a tumor suppressor function for HER4, however, a molecular mechanism to explain the selective loss of HER4 expression has remained elusive. Epigenetic mechanisms, for example, aberrant gene promoter hypermethylation, have been shown to ablate tumor suppressor gene expression in breast carcinomas. We identified a CpG island within the HER4 promoter and show by pyrosequencing of bisulfite-treated DNA an inverse correlation between HER4 expression and the extent of promoter methylation. Treatment of the HER4-negative BT20 cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine (DAC)-enhanced HER4 expression, conf

SUBMITTER: Das PM 

PROVIDER: S-EPMC3007096 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature