Tags

Type your tag names separated by a space and hit enter

Renal cancer cells lacking hypoxia inducible factor (HIF)-1alpha expression maintain vascular endothelial growth factor expression through HIF-2alpha.
Carcinogenesis. 2007 Mar; 28(3):529-36.C

Abstract

Recent efforts have been aimed at targeting the hypoxia inducible factor (HIF)-mediated hypoxia-induced gene pathway for renal cell carcinomas (RCC) therapy. Among the various genes induced by HIF, vascular endothelial growth factor (VEGF) is one of the critical mediators in angiogenesis, tumor growth and metastasis. To date, however, limited information is available on the functional differences regarding VEGF transcription between the HIF subunits, namely HIF-1alpha and HIF-2alpha. To investigate the HIF-1alpha and HIF-2alpha-dependent effect on VEGF gene induction in RCC, a panel of human RCC cell lines was analyzed. We found that a loss of HIF-1alpha protein expression was a common event in RCC cell lines, which was associated not only with truncated HIF-1alpha mRNA transcripts but also with transcriptional silencing. Since the CpG rich promoter region of the HIF-1alpha gene contained a similar frequency of methylated CpG dinucleotides in RCC cell lines, a complex and non-uniform mechanism may be involved in this phenomenon. In these HIF-1alpha defective cell lines, the knockdown of the HIF-2alpha gene demonstrated that HIF-2alpha regulated the VEGF production, irrespective of the VHL gene mutation status. In contrast, HIF-1alpha played a predominant role in VEGF secretion in the cells expressing both wild-type HIF-1alpha and HIF-2alpha proteins. HIF-1alpha may therefore represent an important target molecule for RCC therapy; however, HIF-2alpha should be targeted in HIF-1alpha defective renal cancer cells.

Authors+Show Affiliations

Department of Urology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16920734

Citation

Shinojima, Toshiaki, et al. "Renal Cancer Cells Lacking Hypoxia Inducible Factor (HIF)-1alpha Expression Maintain Vascular Endothelial Growth Factor Expression Through HIF-2alpha." Carcinogenesis, vol. 28, no. 3, 2007, pp. 529-36.
Shinojima T, Oya M, Takayanagi A, et al. Renal cancer cells lacking hypoxia inducible factor (HIF)-1alpha expression maintain vascular endothelial growth factor expression through HIF-2alpha. Carcinogenesis. 2007;28(3):529-36.
Shinojima, T., Oya, M., Takayanagi, A., Mizuno, R., Shimizu, N., & Murai, M. (2007). Renal cancer cells lacking hypoxia inducible factor (HIF)-1alpha expression maintain vascular endothelial growth factor expression through HIF-2alpha. Carcinogenesis, 28(3), 529-36.
Shinojima T, et al. Renal Cancer Cells Lacking Hypoxia Inducible Factor (HIF)-1alpha Expression Maintain Vascular Endothelial Growth Factor Expression Through HIF-2alpha. Carcinogenesis. 2007;28(3):529-36. PubMed PMID: 16920734.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renal cancer cells lacking hypoxia inducible factor (HIF)-1alpha expression maintain vascular endothelial growth factor expression through HIF-2alpha. AU - Shinojima,Toshiaki, AU - Oya,Mototsugu, AU - Takayanagi,Atsushi, AU - Mizuno,Ryuichi, AU - Shimizu,Nobuyoshi, AU - Murai,Masaru, Y1 - 2006/08/18/ PY - 2006/8/22/pubmed PY - 2007/9/15/medline PY - 2006/8/22/entrez SP - 529 EP - 36 JF - Carcinogenesis JO - Carcinogenesis VL - 28 IS - 3 N2 - Recent efforts have been aimed at targeting the hypoxia inducible factor (HIF)-mediated hypoxia-induced gene pathway for renal cell carcinomas (RCC) therapy. Among the various genes induced by HIF, vascular endothelial growth factor (VEGF) is one of the critical mediators in angiogenesis, tumor growth and metastasis. To date, however, limited information is available on the functional differences regarding VEGF transcription between the HIF subunits, namely HIF-1alpha and HIF-2alpha. To investigate the HIF-1alpha and HIF-2alpha-dependent effect on VEGF gene induction in RCC, a panel of human RCC cell lines was analyzed. We found that a loss of HIF-1alpha protein expression was a common event in RCC cell lines, which was associated not only with truncated HIF-1alpha mRNA transcripts but also with transcriptional silencing. Since the CpG rich promoter region of the HIF-1alpha gene contained a similar frequency of methylated CpG dinucleotides in RCC cell lines, a complex and non-uniform mechanism may be involved in this phenomenon. In these HIF-1alpha defective cell lines, the knockdown of the HIF-2alpha gene demonstrated that HIF-2alpha regulated the VEGF production, irrespective of the VHL gene mutation status. In contrast, HIF-1alpha played a predominant role in VEGF secretion in the cells expressing both wild-type HIF-1alpha and HIF-2alpha proteins. HIF-1alpha may therefore represent an important target molecule for RCC therapy; however, HIF-2alpha should be targeted in HIF-1alpha defective renal cancer cells. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/16920734/Renal_cancer_cells_lacking_hypoxia_inducible_factor__HIF__1alpha_expression_maintain_vascular_endothelial_growth_factor_expression_through_HIF_2alpha_ L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/bgl143 DB - PRIME DP - Unbound Medicine ER -