Overexpression of vacuolar ATPase 16-kDa subunit in 10T1/2 fibroblasts enhances invasion with concomitant induction of matrix metalloproteinase-2.
Recent studies show that the vacuolar-type H(+)-ATPase (V-ATPase) 16 kDa subunit is expressed on plasma membrane of cancer cells. We hypothesized that V-ATPase 16 kDa subunit is directly involved in cell invasion. In the present study we established transfectants overexpressing V-ATPase 16 kDa subunit at the mRNA level, and found that these transfectants showed an enhanced invasiveness through matrigel with a concomitant increases in secretion of matrix metalloproteinase-2. Moreover, antisense oligonucleotides of the V-ATPase 16 kDa subunit suppressed invasive human A549 cell invasion with concomitant decreases in secretion of matrix metalloproteinase-2. The results suggest that the V-ATPase 16 kDa subunit is directly involved in cell invasion and that matrix metalloproteinase-2 is responsible for promoting the invasion by the V-ATPase 16 kDa subunit.
Kubota
S
S
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan. kubota@bio.m.u-tokyo.ac.jp
Seyama
Y
Y
D000818:Animals; D002460:Cell Line; D004790:Enzyme Induction; D005347:Fibroblasts / Q000201:enzymology / Q000648:ultrastructure; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D051379:Mice; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025262:Vacuolar Proton-Translocating ATPases
D016376:Oligonucleotides, Antisense; D020778:Matrix Metalloproteinase 2; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases