RASSF1C modulates the expression of a stem cell renewal gene, PIWIL1

BMC Research Notes

Yousef G Amaar¹  Subburaman Mohan³  Xinmin Li²  Shin-Tai Chen³  Scott Baldwin¹  Robert Aragon¹  Melissa L Baldwin⁴  Mark E Reeves¹ 

[1] Department of Surgery, Loma Linda University School of Medicine, Loma Linda, CA, USA;Department of Pathology, University of California, Los Angeles, CA, USA;Musculoskeletal Disease Center, Loma Linda VA Medical Center, Loma Linda, CA, USA;Surgical Oncology Laboratory, Loma Linda VA Medical Center, 11201 Benton Street (151), Loma Linda, CA 92357, USA

关键词: ERK1/2;    RASSF1C target genes;    Gene expression;    PIWIL1;    RASSF1C;   

Others  :  1166418
DOI  :  10.1186/1756-0500-5-239

 received in 2011-10-13, accepted in 2012-04-02,  发布年份 2012

【 摘 要 】

Background

RASSF1A and RASSF1C are two major isoforms encoded by the Ras association domain family 1 (RASSF1) gene through alternative promoter selection and mRNA splicing. RASSF1A is a well established tumor suppressor gene. Unlike RASSF1A, RASSF1C appears to have growth promoting actions in lung cancer. In this article, we report on the identification of novel RASSF1C target genes in non small cell lung cancer (NSCLC).

Methods

Over-expression and siRNA techniques were used to alter RASSF1C expression in human lung cancer cells, and Affymetrix-microarray study was conducted using NCI-H1299 cells over-expressing RASSF1C to identify RASSF1C target genes.

Results

The microarray study intriguingly shows that RASSF1C modulates the expression of a number of genes that are involved in cancer development, cell growth and proliferation, cell death, and cell cycle. We have validated the expression of some target genes using qRT-PCR. We demonstrate that RASSF1C over-expression increases, and silencing of RASSF1C decreases, the expression of PIWIL1 gene in NSCLC cells using qRT-PCR, immunostaining, and Western blot analysis. We also show that RASSF1C over-expression induces phosphorylation of ERK1/2 in lung cancer cells, and inhibition of the MEK-ERK1/2 pathway suppresses the expression of PIWIL1 gene expression, suggesting that RASSF1C may exert its activities on some target genes such as PIWIL1 through the activation of the MEK-ERK1/2 pathway. Also, PIWIL1 expression is elevated in lung cancer cell lines compared to normal lung epithelial cells.

Conclusions

Taken together, our findings provide significant data to propose a model for investigating the role of RASSF1C/PIWIL1 proteins in initiation and progression of lung cancer.

【 授权许可】

   
2012 Reeves et al.; licensee BioMed Central Ltd

【 图 表 】

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