| First Author | Sueoka E | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 4 | Pages | e57833 |
| PubMed ID | 23593116 | Mgi Jnum | J:200040 |
| Mgi Id | MGI:5506853 | Doi | 10.1371/journal.pone.0057833 |
| Citation | Sueoka E, et al. (2013) Development of lymphoproliferative diseases by hypoxia inducible factor-1alpha is associated with prolonged lymphocyte survival. PLoS One 8(4):e57833 |
| abstractText | Hypoxia-inducible factor-1alpha (HIF-1 alpha) plays an essential role in the regulation of various genes associated with low oxygen consumption. Elevated expression of HIF-1alpha has been reported to be associated with tumor progression, invasion and metastasis in many cancers. To investigate the role of HIF-1alpha in tumor development and metastasis, we established transgenic mice constitutively expressing HIF1A gene under regulation of the cytomegalovirus gene promoter. Although HIF-1alpha protein levels varied among organs, expression of HIF1A mRNA in most organs gradually increased in an age-dependent manner. The transgenic mice showed no gross morphological abnormality up to 8 weeks after birth, although they subsequently developed tumors in the lymphoid, lung, and breast; the most prominent tumor was lymphoma appearing in the intestinal mucosa and intra-mesenchymal tissues. The prevalence of tumors reached 80% in 13 months after birth. The constitution of lymphocyte populations in the transgenic mice did not differ from that in wild-type mice. However, lymphocytes of the transgenic mice revealed prolonged survival under long-term culture conditions and revealed increased resistance to cytotoxic etoposide. These results suggest that HIF-1alpha itself is not oncogenic but it may play an important role in lymphomagenesis mediated through the prolonged survival of lymphocytes in this transgenic mouse model. |
