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. Copyright 2001 Academic Press.