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Regulation of Matrix Metalloproteinases and Invasion by Gα12/13 Proteins in NIH3T3 Mouse Fibroblast Cells

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Abstract:

The G12 subfamily of the heterotrimeric G proteins, Gα12 and Gα13, has been implicated as an important signaling component in various cellular processes including oncogenesis and cells invasion. Our previous report showed that the expression of an activated mutant of Gα12 (Gα12QL) or Gα13 (Gα13QL) leads to cell invasion in MCF10A human breast epithelial cells. The present study aimed to investigate the role of Gα12 and Gα13 in the malignant phenotypic conversion of NIH3T3 mouse fibroblast cells. Gα12QL and Gα13QL induced an invasive phenotype in NIH3T3 cells. In addition, the activation of Gα12 and Gα13 upregulated matrix metalloproteinase (MMP)-2 while MMP-9 was not affected by either Gα12QL or Gα13QL. Using female NOD/SCID mice injected with NIH3T3 cells stably expressing Gα12QL, we provided in vivo confirmation of Gα12-mediated MMP-2 upregulation. Taken together, this study elucidated the role of Gα12/13 in regulating malignant phenotypic conversion of NIH3T3 fibroblast cells, validating the role of Gα12/13 in tumorigenesis.

Keywords: Cell invasion; Gα12/13; Matrix metalloproteinase-2 (MMP-2)

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096504011X13021877989919

Publication date: June 1, 2011

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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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