Dataset Information

The RasGAP gene, RASAL2, is a tumor and metastasis suppressor.

ABSTRACT: RAS genes are commonly mutated in cancer; however, RAS mutations are rare in breast cancer, despite frequent hyperactivation of Ras and ERK. Here, we report that the RasGAP gene, RASAL2, functions as a tumor and metastasis suppressor. RASAL2 is mutated or suppressed in human breast cancer, and RASAL2 ablation promotes tumor growth, progression, and metastasis in mouse models. In human breast cancer, RASAL2 loss is associated with metastatic disease; low RASAL2 levels correlate with recurrence of luminal B tumors; and RASAL2 ablation promotes metastasis of luminal mouse tumors. Additional data reveal a broader role for RASAL2 inactivation in other tumor types. These studies highlight the expanding role of RasGAPs and reveal an alternative mechanism of activating Ras in cancer.

SUBMITTER: McLaughlin SK

PROVIDER: S-EPMC3822334 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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The RasGAP gene, RASAL2, is a tumor and metastasis suppressor.

McLaughlin Sara Koenig SK Olsen Sarah Naomi SN Dake Benjamin B De Raedt Thomas T Lim Elgene E Bronson Roderick Terry RT Beroukhim Rameen R Polyak Kornelia K Brown Myles M Kuperwasser Charlotte C Cichowski Karen K

Cancer cell 20130901 3

RAS genes are commonly mutated in cancer; however, RAS mutations are rare in breast cancer, despite frequent hyperactivation of Ras and ERK. Here, we report that the RasGAP gene, RASAL2, functions as a tumor and metastasis suppressor. RASAL2 is mutated or suppressed in human breast cancer, and RASAL2 ablation promotes tumor growth, progression, and metastasis in mouse models. In human breast cancer, RASAL2 loss is associated with metastatic disease; low RASAL2 levels correlate with recurrence of ...[more]

PMID: 24029233

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Project description:Background: Tetraspanin CD82 is a tumor metastasis suppressor that is known to down regulate in various metastatic cancers. However, the exact mechanism by which CD82 prevents cancer metastasis is unclear. This study aims to identify genes that are regulated by CD82 in human prostate cell lines.Methods: We used whole human genome microarray to obtain gene expression profiles in a normal prostate epithelial cell line that expressed CD82 (PrEC-31) and a metastatic prostate cell line that does not express CD82 (PC3). Then, siRNA silencing was used to knock down CD82 expression in PrEC-31 while CD82 was re-expressed in PC3 to acquire differentially-expressed genes in the respective cell line.Results: Differentially-expressed genes with a P?<?0.05 were identified in 3 data sets: PrEC-31 (+CD82) vs PrEC-31(-CD82), PC3-57 (+CD82) vs. PC3-5?V (-CD82), and PC3-29 (+CD82) vs. PC3-5?V (-CD82). Top 25 gene lists did not show overlap within the data sets, except (CALB1) the calcium binding protein calbindin 1 which was significantly up-regulated (2.8 log fold change) in PrEC-31 and PC3-29 cells that expressed CD82. Other most significantly up-regulated genes included serine peptidase inhibitor kazal type 1 (SPINK1) and polypeptide N-acetyl galactosaminyl transferase 14 (GALNT14) and most down-regulated genes included C-X-C motif chemokine ligand 14 (CXCL14), urotensin 2 (UTS2D), and fibroblast growth factor 13 (FGF13). Pathways related with cell proliferation and angiogenesis, migration and invasion, cell death, cell cycle, signal transduction, and metabolism were highly enriched in cells that lack CD82 expression. Expression of two mutually inclusive genes in top 100 gene lists of all data sets, runt-related transcription factor (RUNX3) and trefoil factor 3 (TFF3), could be validated with qRT-PCR.Conclusion: Identification of genes and pathways regulated by CD82 in this study may provide additional insights into the role that CD82 plays in prostate tumor progression and metastasis, as well as identify potential targets for therapeutic intervention.

Dataset Information

The RasGAP gene, RASAL2, is a tumor and metastasis suppressor.

Publications

The RasGAP gene, RASAL2, is a tumor and metastasis suppressor.

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