title: Regulation of matrix metalloproteinases and invasion by G(alpha12/13) proteins in NIH3T3 mouse fibroblast cells.
abstract: The G12 subfamily of the heterotrimeric G proteins, Galpha12 and Galpha13, 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 Galpha12 (Galpha12QL) or Galpha13 (Galpha13QL) leads to cell invasion in MCF10A human breast epithelial cells. The present study aimed to investigate the role of Galpha12 and Galpha13 in the malignant phenotypic conversion of NIH3T3 mouse fibroblast cells. Galpha12QL and Galpha13QL induced an invasive phenotype in NIH3T3 cells. In addition, the activation of Galpha12 and Galpha13 upregulated matrix metalloproteinase (MMP)-2 while MMP-9 was not affected by either Galpha12QL or Galpha13QL. Using female NOD/SCID mice injected with NIH3T3 cells stably expressing Galpha12QL, we provided in vivo confirmation of Galpha12-mediated MMP-2 upregulation. Taken together, this study elucidated the role of Galpha12/13 in regulating malignant phenotypic conversion of NIH3T3 fibroblast cells, validating the role of Galphal2/13 in tumorigenesis.
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul, Korea.
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Kim
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Noh
authors.forename: Aree
authors.initials: A
authors.lastname: Moon
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D005260:Female; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D044365:GTP-Binding Protein alpha Subunits, G12-G13