Effect of hypoxia on human seminoma cells.
Since hypoxia has been considered to enhance metastatic potential in solid tumors via a neo-angiogenesis caused by vascular endothelial cell growth factors (VEGFs) induced by hypoxia inducible factor-1alpha (HIF-1alpha), the effects of hypoxia on human seminoma cell lines were examined in terms of growth, morphology, gene expression, protein expression and cell cycle perturbation. Growth was inhibited in long-term cultures with morphological changes to the spindle form. The gene expression of VEGF-C was markedly enhanced and the production of VEGF-A increased during hypoxia, although HIF-1alpha was not upregulated at the protein or message level. Hypoxic culture caused G1 cell cycle arrest with upregulation of the p15/ink4b and p27/Kip1 genes, whereas no increase of apoptotic cells was observed on up-regulation of the heat shock protein (HSP) 70 gene. The adhesion molecules were only slightly altered.
Fujii
Tomohiro
T
Department of Urology, Kawasaki Medical School, Okayama 701-0192, Japan.
Otsuki
Takemi
T
Moriya
Takuya
T
Sakaguchi
Haruko
H
Kurebayashi
Junichi
J
Yata
Kenichiro
K
Uno
Masako
M
Kobayashi
Tatsuya
T
Kimura
Takahiro
T
Jo
Yoshimasa
Y
Kinugawa
Keigo
K
Furukawa
Yoji
Y
Morioka
Masaaki
M
Ueki
Ayako
A
Tanaka
Hiroyoshi
H
D017209:Apoptosis; D002448:Cell Adhesion; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018076:DNA, Complementary / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D005434:Flow Cytometry; D016193:G1 Phase; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D000860:Hypoxia; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008207:Lymphatic Metastasis; D008297:Male; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018239:Seminoma / Q000378:metabolism* / Q000473:pathology; D013736:Testicular Neoplasms / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C
C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D018840:HSP70 Heat-Shock Proteins; D018960:Hyaluronan Receptors; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D018799:Intercellular Adhesion Molecule-1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012313:RNA