Radixin is a member of the ERM (
ezrin/
radixin/
moesin)
protein family that is proposed to function as a membrane-cytoskeletal linker. Using differential display analysis, we have identified
radixin as a gene down-regulated in primary
lung adenocarcinoma. Real-time quantitative reverse transcription polymerase chain reaction confirmed that
radixin mRNA was decreased, both in 10 early-stage
bronchioloalveolar carcinomas and in 16 invasive
lung adenocarcinomas, by 69% (p = 0.0002) and 82% (p < 0.0001), respectively, compared with 9 nontumor lung tissues. Similarly,
moesin and
ezrin mRNA levels were reduced in
lung adenocarcinoma. Immunohistochemistry confirmed that
cancer cells expressed very little
radixin and
moesin, whereas non-neoplastic alveolar and bronchiolar epithelial cells, and endothelial cells, including those within the
tumor stroma, were consistently positive for these two
proteins.
Ezrin was localized in the apical surface of non-neoplastic bronchiolar and alveolar epithelial cells and, in contrast to
radixin and
moesin, the majority of
tumor cells retained expression of
ezrin. Localization of
ezrin was altered in a significant proportion of
tumor cells: whereas
tumor cells forming lumina displayed membranous staining on the apical side,
tumor cells with disorganized structures were either negative or diffusely positive for
ezrin in the cytoplasm. Furthermore, a fraction of
tumor cells invading the stroma in a scattered manner were strongly positive for
ezrin. In conclusion, expression of
radixin and
moesin is down-regulated in
lung adenocarcinoma, including early-stage
bronchioloalveolar carcinoma. An intriguing implication of this finding is that these two genes may function as
tumor suppressors in
lung adenocarcinoma oncogenesis. Although structurally related to
radixin and
moesin,
ezrin may have a distinct function in
tumor-cell invasion.