Altered expression of the ERM proteins in lung adenocarcinoma

Radixin is a member of the ERM (ezrin/radixin/moesin) protein family that i s proposed to function as a membrane-cytoskeletal linker. Using differentia l display analysis, we have identified radixin as a gene down-regulated in primary lung adenocarcinoma. Real-time quantitative reverse transcription p olymerase chain reaction confirmed that radixin mRNA was decreased, both in 10 early-stage bronchioloalveolar carcinomas and in 16 invasive lung adeno carcinomas, by 69% (p = 0.0002) and 82% (p < 0.0001), respectively, compare d with 9 nontumor lung tissues. Similarly, moesin and ezrin mRNA levels wer e reduced in lung adenocarcinoma. Immunohistochemistry confirmed that cance r cells expressed very little radixin and moesin, whereas non-neoplastic al veolar and bronchiolar epithelial cells, and endothelial cells, including t hose within the tumor stroma, were consistently positive for these two prot eins. Ezrin was localized in the apical surface of non-neoplastic bronchiol ar and alveolar epithelial cells and, in contrast to radixin and moesin, th e majority of tumor cells retained expression of ezrin. Localization of ezr in was altered in a significant proportion of tumor cells: whereas tumor ce lls forming lumina displayed membranous staining on the apical side, tumor cells with disorganized structures were either negative or diffusely positi ve for ezrin in the cytoplasm. Furthermore, a fraction of tumor cells invad ing the stroma in a scattered manner were strongly positive for ezrin. In c onclusion, expression of radixin and moesin is down-regulated in lung adeno carcinoma, including early-stage bronchioloalveolar carcinoma. An intriguin g implication of this finding is that these two genes may function as tumor suppressors in lung adenocarcinoma oncogenesis. Although structurally rela ted to radixin and moesin, ezrin may have a distinct function in tumor-cell invasion.