PMID- 22591718 OWN - NLM STAT- MEDLINE DCOM- 20130523 LR - 20220330 IS - 1756-0500 (Electronic) IS - 1756-0500 (Linking) VI - 5 DP - 2012 May 16 TI - RASSF1C modulates the expression of a stem cell renewal gene, PIWIL1. PG - 239 LID - 10.1186/1756-0500-5-239 [doi] AB - 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. FAU - Reeves, Mark E AU - Reeves ME AD - Surgical Oncology Laboratory, Loma Linda VA Medical Center, CA 92357, USA. FAU - Baldwin, Melissa L AU - Baldwin ML FAU - Aragon, Robert AU - Aragon R FAU - Baldwin, Scott AU - Baldwin S FAU - Chen, Shin-Tai AU - Chen ST FAU - Li, Xinmin AU - Li X FAU - Mohan, Subburaman AU - Mohan S FAU - Amaar, Yousef G AU - Amaar YG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120516 PL - England TA - BMC Res Notes JT - BMC research notes JID - 101462768 RN - 0 (2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide) RN - 0 (Argonaute Proteins) RN - 0 (Benzamides) RN - 0 (PIWIL1 protein, human) RN - 0 (RASSF1 protein, human) RN - 0 (Tumor Suppressor Proteins) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Apoptosis/genetics MH - Argonaute Proteins/*genetics/metabolism MH - Benzamides/pharmacology MH - Blotting, Western MH - Carcinoma, Non-Small-Cell Lung/genetics/metabolism/pathology MH - Cell Cycle/genetics MH - Cell Line MH - Cell Line, Tumor MH - Cell Proliferation MH - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/metabolism MH - Gene Expression Profiling MH - Gene Expression Regulation, Neoplastic/drug effects/*genetics MH - Humans MH - Immunohistochemistry MH - Lung Neoplasms/genetics/metabolism/pathology MH - MAP Kinase Signaling System/drug effects MH - Neoplastic Stem Cells/*metabolism MH - Oligonucleotide Array Sequence Analysis MH - Phosphorylation/drug effects MH - RNA Interference MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Suppressor Proteins/*genetics/metabolism PMC - PMC3512503 EDAT- 2012/05/18 06:00 MHDA- 2013/05/25 06:00 PMCR- 2012/05/16 CRDT- 2012/05/18 06:00 PHST- 2011/10/13 00:00 [received] PHST- 2012/04/02 00:00 [accepted] PHST- 2012/05/18 06:00 [entrez] PHST- 2012/05/18 06:00 [pubmed] PHST- 2013/05/25 06:00 [medline] PHST- 2012/05/16 00:00 [pmc-release] AID - 1756-0500-5-239 [pii] AID - 10.1186/1756-0500-5-239 [doi] PST - epublish SO - BMC Res Notes. 2012 May 16;5:239. doi: 10.1186/1756-0500-5-239.