Abstract 2476: Tumor development in transgenic mice constitutively expressing hypoxia-inducible factor-1α

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Hypoxia-inducible factor-1α (HIF-1α) has an essential transcription factor for regulation of various genes associated with hypoxic condition in tissues. Elevated expression of HIF-1α has been reported in many cancers associated with tumor progression, invasion and metastasis. To investigate the role of HIF-1α in tumor development and metastasis, we established transgenic mice constitutively expressing HIF-1α gene under regulation of CMV promoter. The transgenic mice showed no gross morphological abnormality until 3 months after birth, but the mice developed tumors in lymphoid, lung and breast tissues. The incidence of tumor bearing in transgenic mice was up to 90% until 18 months after birth. Expression of HIF-1α mRNA and protein was varied among tissues, but the amount of HIF-1α gene was gradually increased in an age-dependent manner. To clarify the molecular mechanism of lymphomagenesis in the transgenic mice, subpopulation of the lymphocytes, mitogenic responsiveness and cytokine production on lymphocyte from transgenic mice were analyzed. We next analyzed the expression of HIF-1α in human lymphoma tissues and found apparent expression of the gene in angioimmunoblastic T cell lymphoma (AILT). Since VEGF expression and marked increase of small vessels in tumor tissues are common features in AILT, HIF-1α may play an important role in pathogenesis of the lymphoma. We present the results concerning the role of HIF-1α in lymphoma occurrence, and will discuss the contribution of the transcription factor in human cancer development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2476.