Hypoxia-inducible factor 1alpha and 1beta proteins share common signaling pathways in human prostate cancer cells.
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor consisting alpha and beta subunits. It is critically involved in cancer cell hypoxia adaptation, glycolysis, and angiogenesis. HIF-1beta is associated with HIF-1 functions as a dimerization partner of HIF-1alpha, and is on the other hand associated with carcinogenesis via dioxin signaling. Regulation of HIF-1beta protein expression was investigated in human prostate cancer (PCA) cells. HIF-1beta protein was expressed constitutively under nonhypoxic conditions in all human PCA cells tested, and was up-regulated by hypoxia, CoCl2, EGF, serum, or PMA in moderate levels. Compared to that of HIF-1alpha, the constitutive, serum-, EGF-, and PMA-increased HIF-1beta protein expression were also inhibited by selective PI3K or FRAP/TOR inhibitors but in higher doses. Hypoxia partially reversed the dose dependent inhibition of HIF-1beta. These results suggest that HIF-1alpha and beta share common signaling pathways for nuclear protein accumulation.
Zhong
H
H
Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA. hua_zhong@emory.org
Hanrahan
C
C
van der Poel
H
H
Simons
J W
JW
D001798:Blood Proteins / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002352:Carrier Proteins; D015687:Cell Hypoxia / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020104:Immunophilins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017853:Phosphotransferases (Alcohol Group Acceptor); D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D021122:Protein Subunits; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D001798:Blood Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D021122:Protein Subunits; D014157:Transcription Factors; D003035:Cobalt; D004815:Epidermal Growth Factor; D017853:Phosphotransferases (Alcohol Group Acceptor); C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020104:Immunophilins; C018021:cobaltous chloride; D013755:Tetradecanoylphorbol Acetate