LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast and colorectal cancer

D. C T Ong, Y. M. Ho, C. Rudduck, Kwang-Yung Chin, W. L. Kuo, D. K H Lie, C. L M Chua, P. H. Tan, K. W. Eu, F. Seow-Choen, C. Y. Wong, G. S. Hong, Joe Gray, A. S G Lee

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Deletion of 11q23-q24 is frequent in a diverse variety of malignancies, including breast and colorectal carcinoma, implicating the presence of a tumor suppressor gene at that chromosomal region. We examined a 6-Mb region on 11q23 by high-resolution deletion mapping, using both loss of heterozygosity analysis and customized microarray comparative genomic hybridization. LARG (leukemia-associated Rho guanine-nucleotide exchange factor) (also called ARHGEF12), identified from the analysed region, is frequently underexpressed in breast and colorectal carcinomas with a reduced expression observed in all breast cancer cell lines (n11), in 12 of 38 (32%) primary breast cancers, 5 of 10 (50%) colorectal cell lines and in 20 of 37 (54%) primary colorectal cancers. Underexpression of the LARG transcript was significantly associated with genomic loss (P0.00334). Hypermethylation of the LARG promoter was not detected in either breast or colorectal cancer, and treatment of four breast and four colorectal cancer cell lines with 5-aza-2′-deoxycytidine and/or trichostatin A did not result in a reactivation of LARG. Enforced expression of LARG in breast and colorectal cancer cells by stable transfection resulted in reduced cell proliferation and colony formation, as well as in a markedly slower cell migration rate in colorectal cancer cells, providing functional evidence for LARG as a candidate tumor suppressor gene.

Original languageEnglish (US)
Pages (from-to)4189-4200
Number of pages12
JournalOncogene
Volume28
Issue number47
DOIs
Publication statusPublished - Nov 2009
Externally publishedYes

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Keywords

  • Breast cancer
  • Colorectal cancer
  • LARG
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Ong, D. C. T., Ho, Y. M., Rudduck, C., Chin, K-Y., Kuo, W. L., Lie, D. K. H., ... Lee, A. S. G. (2009). LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast and colorectal cancer. Oncogene, 28(47), 4189-4200. https://doi.org/10.1038/onc.2009.266