A Study on the Molecular Phenotype of Human Lung Adenocarcinoma Stem Cells and Biological Functions of PLAGL2 Gene

Abstract: Emerging evidence indicated that tumors originated from malignant transformation of tissueresident stem cells and/or progenitor cells. These transformed stem/progenitor cells are named as tumor-initiating cells or cancer stem cells (CSC). However， the potential cell origion of CSC in lung cancer remains unclear at present. We reported the existance of OCT4-expressing BASC (bronchiolaveolar stem cells)-like CSC in human lung adenocarcinoma. With the technique of RNA interfering， we inactivated the expression of PLAGL2 (pleiomorphic adenoma gene-like 2)， a gene encoding the zinc finger transcription factors， in the CSC of lung adenocarcinoma. The results demonstrated that knockdown of PLAGL2 enforced the cells to differentiate into the AT1 (alveolar type 1) cell-like state and lost the tumorigenic ability. With the plateform of microarray (gene chip) screening， we showed that the CSC in lung adenocarcinoma shared molecular phenotypes with the undifferentiated stem cells and the alveolar progenitor cells of human lung， suggesting these primitive cells as a promising cell origion of CSC in lung adenocarcinoma. In addition， the results presented herein revealed that the differentiation of CSC in lung adenocarcinoma was under the dural control of TTF-1 (thyroid transcription factor-1) and PLAGL2. By gene menagment and pharmacolical induction， these CSCs were able to differentiate. These studies provided a novel evanue for CSC-targeted therapies in lung cancer.

CSTR: 32200.14.cjcb.2012.04.0009