Hypoxia-inducible factor 1 alpha and 1 beta 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 cel l hypoxia adaptation, glycolysis, and angiogenesis. HIF-1 beta is associate d with HIF-1 functions as a dimerization partner of HIF-1 alpha, and is on the other hand associated with carcinogenesis via dioxin signaling. Regulat ion of HIF-1 beta protein expression was investigated in human prostate can cer (PCA) cells. HIF-1 beta protein was expressed constitutively under nonh ypoxic conditions in all human PCA cells tested, and was up-regulated by hy poxia, CoCl2 EGF, serum, or PMA in moderate levels. Compared to that of HIF -1 alpha, the constitutive, serum-, EGF-, and PMA-increased HIF-1 beta prot ein expression were also inhibited by selective P13K or FRAP/TOR inhibitors but in higher doses. Hypoxia partially reversed the dose dependent inhibit ion of HIF-1 beta. These results suggest that HIF-1 alpha and beta share co mmon signaling pathways for nuclear protein accumulation. (C) 2001 Academic Press.