Moesin expression is associated with the estrogen receptor-negative breast cancer phenotype.

ABSTRACT

BACKGROUND: Estrogen receptor (ER)-positive breast carcinomas possess a less aggressive phenotype than ER-negative breast carcinomas. We hypothesize that a set of genes exists that is expressed only in ER-negative breast carcinomas, which account for the more malignant phenotypic characteristics of these tumors. METHODS: We have used a new technique of polymerase chain reaction select suppression subtractive hybridization to identify genes that are expressed only in ER-negative carcinomas. RESULTS: Seventy-one cDNA clones generated by suppression subtractive hybridization were screened by Northern blot analysis with RNA from ER-positive MCF7 and ER-negative MDA-MB-231 breast carcinoma cell lines. Fifteen clones were differentially expressed in MDA-MB-231 cells. Five of these 15 clones were consistently found to be associated with the ER-negative phenotype in a panel of eight breast carcinoma cell lines. Sequence analysis demonstrated that three of these clones were derived from vimentin and two clones from moesin. Western blot analysis with antihuman moesin antibody confirmed that moesin protein was overexpressed in ER-negative breast carcinoma cell lines but absent from ER-positive breast carcinomas. Moesin mRNA was examined in a panel of 29 primary breast carcinomas with semi-quantitative reverse transcriptase-polymerase chain reaction. Moesin expression was found to be decreased significantly in ER-positive compared with ER-negative tumors (P < .01). CONCLUSIONS: Vimentin and moesin are differentially expressed in association with the ER-negative breast cancer phenotype. Moesin is a membrane/actin filament protein involved in dynamic restructuring of the cell surface and filopodia, a cell structure needed for cell adhesion and motility. Moesin may play a role in the invasiveness and pattern of metastasis characteristic of ER-negative breast cancers.