MOESIN EXPRESSION IS ASSOCIATED WITH THE ESTROGEN RECEPTOR-NEGATIVE BREAST-CANCER PHENOTYPE

Background. Estrogen receptor(FR)positive breast carcinomas possess a less aggressive phenotype than ER-negative breast carcinomas. We hypot hesize that a set of genes exists that is expressed only in ER-negativ e breast carcinomas, which account for the more malignant phenotypic c haracteristics of these tumors. Methods, We have used a new technique of polymerase chain reaction select suppression subtractive hybridizat ion to identify genes that are expressed only in ER-negative carcinoma s. Results, Seventy-one cDNA clones generated by suppression subtracti ve hybridization were screened by Northern blot analysis with RNA from ER-positive MCF7 and ER-negative MDA-MB-231 breast carcinoma cell lin es. 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 li nes. Sequence analysis demonstrated that three of these clones were de rived from vimentin and two clones from moesin. Western blot analysis with antihuman moesin antibody confirmed that moesin protein was overe xpressed 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 transcriptas e-polymerase chain reaction, Moesin expression was found to be decreas ed significantly in ER-positive compared with ER-negative tumors (P < .01). Concusions, 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 t he cell surface and filopodia, a cell structure needed for cell adhesi on and motility. Moesin may play a role in the invasiveness and patter n of metastasis characteristic of ER-negative breast cancers..