The Role of PITX2B in Non-Small-Cell Lung Cancer

• Main Authors: Yu-Han Huang, 黃宇涵
• Other Authors: Jeremy J.W Chen
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/86366754464194927328

碩士 === 國立中興大學 === 分子生物學研究所 === 99 === Non-small-cell lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death with high risk. In our previous study demonstrated that knockdown of HLJ1, a novel tumor suppressor gene, increased PITX2 expression, suggesting that PITX2 may promote the tumorigenic ability of non-small-cell lung cancer. PITX2 (paired-like homeodomain transcription factor 2) is involved in the development of the eye, tooth and abdominal organs. This gene is a member of the bicoid-homeodomain class of transcription factors implicated in controlling left-right asymmetry during organogenesis. Three transcript variants encoding distinct isoforms have been identified for this gene. In our study, we found that PITX2B was the major isoform frequently expressed in the aggressive lung cancer cell lines. Furthermore, overexpression of PITX2B in CL1-0 could enhance the ability of invasion、migration、proliferation and tumorigenesis in human non-small-cell lung cancer. In addition, we performed site-direct mutagenesis at the NLS (nuclear localization signal) of PITX2B to generate the PITX2B mutants and introduced these constructs to lung cancer cells. Interesting, the results demonstrated that NLS is important for PITX2B to promote cell migration and colony formation activity. However, the underlying molecular mechanism remains to be verified. . On the other side, we used the siRNA (small interference RNA) to silence the expression of PITX2 mRNA, and noticed that silence of PITX2 could induce cell autophagy and lead to cell death. Taken together, the expression of PITX2B is important for non-small-cell lung cancer progression.