Abstract：
:Renal cell carcinoma (RCC) is the most common primary cancer arising from the kidney in adults, with clear cell renal cell carcinoma (ccRCC) representing approximately 75% of all RCCs. Increased expression of the hypoxia-induced factors-1α (HIF1α) and HIF2α has been suggested as a pivotal step in ccRCC carcinogenesis, but this has not been thoroughly tested. Here, we report that expression of a constitutively activated form of HIF2α (P405A, P530A, and N851A, named as HIF2αM3) in the proximal tubules of mice is not sufficient to promote ccRCC by itself, nor does it enhance HIF1αM3 oncogenesis when coexpressed with constitutively active HIF1αM3. Neoplastic transformation in kidneys was not detected at up to 33 months of age, nor was increased expression of Ki67 (MKI67), γH2AX (H2AFX), or CD70 observed. Furthermore, the genome-wide transcriptome of the transgenic kidneys does not resemble human ccRCC. We conclude that a constitutively active HIF2α is not sufficient to cause neoplastic transformation of proximal tubules, arguing against the idea that HIF2α activation is critical for ccRCC tumorigenesis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Fu L,Wang G,Shevchuk MM,Nanus DM,Gudas LJdoi
10.1158/0008-5472.CAN-12-3983subject
Has Abstractpub_date
2013-05-01 00:00:00pages
2916-25issue
9eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-3983journal_volume
73pub_type
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