Caveolin-1 interferes cell growth of lung cancer NCI-H446 cell through the interactions with phospho-ERK1/2, estrogen receptor and progestin receptor

Abstract

Caveolin-1 (CAV-1) either functions as a tumor suppressor gene or as an oncogene depending on the types of tumor cells and tumors. In current work, we investigated the influences of CAV-1 on the proliferation and cell cycle of small cell lung cancer (SCLC) cell NCI-H446, empty vector transfected NCI-H446 (NCI-H446-neo) and wild-type CAV-1 gene stably transfected NCI-H446 (NCI-H446-CAV-1) cells and explored the potential underlying mechanism. The colony formation capacity of NCI-H446-CAV-1 cell was 58.5% of that for NCI-H446 cell and 57.0% of that for NCI-H446-neo cell. CAV-1 inhibited the cell growth and cell cycle distribution of NCI-H446 cell in vitro. CAV-1 over-expression decreased the population of NCI-H446 cell at S phase and blocked NCI-H446 cell at G2/M phase without apparent effect on G1/G0 cell population. The level of phosphoryalted extracellular signal-regulated kinases (p-ERK1/2) instead of whole ERK1/2 in NCI-H446 cell was dramatically decreased following the stable expression of CAV-1. ERK1/2 phosphorylation might be critical for NCI-H446 cell growth. This work also revealed CAV-1 potentially regulated NCI-H446 growth in a hormone-dependant manner. Estrogen receptor (ER) and progestin receptor (PR) were significantly down-regulated in NCI-H446-CAV-1 cell comparing to NCI-H446 and NCI-H446-neo cells. Taken together, CAV-1 affected cell growth of lung cancer NCI-H446 cell through the interactions with p-ERK1/2, ER and PR.