Isolation of a novel mouse gene, mSVS-1/SUSD2, reversing tumorigenic phenotypes of cancer cells in vitro.
We report isolation of a novel tumor-reversing gene, tentatively named SVS-1, encoding a protein of 820 amino acids with localization on the plasma membrane as a type I transmembrane protein. The gene was found among those downregulated in the activated oncogene-v-K-ras-transformed NIH3T3 cells, Ki3T3, with tumorigenic phenotype. SVS-1 protein harbors several functional domains inherent to adhesion molecules. Histochemical staining of mouse tissues using antibody raised against the protein showed the expression of the protein in restricted regions and cells, for example, strongly positive in apical membranes of epithelial cells in renal tubules and bronchial tubes. The protein inducibly expressed in human fibrosarcoma HT1080 cells and cervical carcinoma HeLa cells was found to be localized primarily on the plasma membrane, as stained with antibodies against FLAG tag in the N-terminus and against the C-terminal peptide of the protein. Expression of the protein in cells induced a variety of biological effects on cancer cells: detachment from the substratum and aggregation of cells and growth inhibition in HeLa cells, but no inhibition in non-tumorigenic mouse NIH3T3 cells. Inhibition of clonogenicity, anchorage-independent growth, migration and invasion through Matrigel was also observed. Taken together these results suggest that the SVS-1 gene is a possible tumor-reversing gene.
Sugahara
Tetsuo
T
Department of Bioinformatics, Soka University, Hachioji, Tokyo, Japan.
Yamashita
Yzumi
Y
Shinomi
Masahito
M
Yamanoha
Banri
B
Iseki
Hiroyoshi
H
Takeda
Akihiko
A
Okazaki
Yasushi
Y
Hayashizaki
Yoshihide
Y
Kawai
Kenji
K
Suemizu
Hiroshi
H
Andoh
Toshiwo
T
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism; D006031:Glycosylation; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D010641:Phenotype; D017434:Protein Structure, Tertiary; D014162:Transfection; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C521511:SVS-1 protein, mouse