Homeobox Transcription Factor NKX2-1 Promotes Transcription in Lung Adenocarcinomas.

Mol Cancer Res 2017 10 20;15(10):1388-1397. Epub 2017 Jun 20.

Department of Molecular Biology, Hamamatsu University School of Medicine, Higashi-ku, Hamamatsu, Shizuoka, Japan.

The known oncogene participates in progression of the cell cycle from G to S-phase. Expression of cyclin D1 is frequently promoted in multiple human cancers including non-small cell lung cancer (NSCLC). However, a relationship between cyclin D1 expression and the prognosis of NSCLC has not been confirmed. NKX2-1 is a homeobox transcription factor involved in pulmonary development as a differentiation-promoting factor. In NSCLC, it acts as a metastasis suppressor and correlates with a good prognosis. Here, NKX2-1-binding motifs were identified in the promoter, but it has not been clarified whether NKX2-1 is involved in cyclin D1 expression in NSCLC. To shed light on this issue, endogenous NKX2-1 was depleted in NSCLC cell lines, which resulted in decreased cyclin D1 mRNA and protein. In contrast, forced overexpression of NKX2-1 increased cyclin D1 levels. Moreover, NKX2-1 directly bound to the promoter and enhanced its activity. Finally, using human NSCLC clinical specimens, it was determined that both NKX2-1 protein and mRNA were significantly correlated with cyclin D1 expression status in adenocarcinomas. These results indicate that NKX2-1 directly and positively regulates transcription of Finally, expression of NKX2-1, but not cyclin D1, was significantly associated with metastatic incidence as an independent good prognostic factor of adenocarcinoma. NKX2-1-expressing adenocarcinomas, whereas NKX2-1 promoted cyclin D1 expression, may show good prognosis features by the metastasis inhibition potency of NKX2-1 regardless cyclin D1 expression. .

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Source
http://mcr.aacrjournals.org/lookup/doi/10.1158/1541-7786.MCR
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http://dx.doi.org/10.1158/1541-7786.MCR-17-0114DOI Listing
October 2017
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