Lrrc46 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Gabrp DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Slc23a1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Tnfrsf11b UP in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Fam46c DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Bpifa2 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Map3k6 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Aoc1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Vpreb3 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Analysis of 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Pklr DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Syt5 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Cldn10 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Cpn2 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Igkv3-12 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Scgb3a1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
1500015O10Rik DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Six4 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Drc1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Cp DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Resp18 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Slc27a2 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Prg2 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Slco1a5 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Mak DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
(Factor value) GENOTYPE/wild type HIF2alpha
Igha DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Mlf1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Dnajb13 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Ltf DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Foxj1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Nme5 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Tff2 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Klf15 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Timp4 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Ifitm6 UP in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Steap4 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Scgb3a2 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Tppp3 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Kcnmb4 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Mycl DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Calml4 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Pigr DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Slc5a1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Iglv1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Tctex1d4 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Zmynd10 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Fank1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Bpifb1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
(Factor value) GENOTYPE/floxed HIF2alpha
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. The oxygen-sensitive Hypoxia Inducible Factor (HIF) transcriptional regulators HIF-1ÃÂÃÂ± and HIF-2ÃÂÃÂ± are overexpressed in many human NSCLCs, and constitutive HIF-2ÃÂÃÂ± activity can promote murine lung tumor progression, suggesting that HIF proteins may be effective NSCLC therapeutic targets. To investigate the consequences of inhibiting HIF activity in lung cancers, we deleted Hif-1ÃÂÃÂ± or Hif-2ÃÂÃÂ± in an established KrasG12D-driven murine NSCLC model. Deletion of Hif-1ÃÂÃÂ± had no obvious effect on tumor growth, whereas Hif-2ÃÂÃÂ± deletion resulted in an unexpected increase in tumor burden that correlated with reduced expression of the candidate tumor suppressor gene Scgb3a1 (HIN-1). Here, we identify Scgb3a1 as a direct HIF-2ÃÂÃÂ± target gene, and demonstrate that HIF-2ÃÂÃÂ± regulates Scgb3a1 expression and tumor formation in human KrasG12D-driven NSCLC cells. AKT pathway activity, reported to be repressed by Scgb3a1, was enhanced in HIF-2ÃÂÃÂ± deficient human NSCLC cells and xenografts. Finally, a direct correlation between HIF-2ÃÂÃÂ± and SCGB3a1 expression was observed in approximately 70% of human NSCLC samples analyzed. These data suggest that whereas HIF-2ÃÂÃÂ± overexpression can contribute to NSCLC progression, therapeutic inhibition of HIF-2ÃÂÃÂ± below a critical threshold may paradoxically promote tumor growth by reducing expression of tumor suppressor genes, including Scgb3a1. RNA was isolated from tumors of experimental (Hif2alpha deficient) mice and control mice (seven for each group).
Aqp4 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Morn3 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Klk11 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Scnn1g DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Muc5b DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Gspt2 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Mok DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Spag6 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Cdhr1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Ereg UP in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
S100b DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Reg3g DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Kif9 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Sncg DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
4933434E20Rik DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Ccna1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Hsph1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Anxa8 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Meig1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Ighg2b DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Adam8 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
St6galnac2 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Ifitm1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Tekt1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Fbxo36 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Chad DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Cidea DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Agr3 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Pon1 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'
Rbp2 DOWN in 'floxed HIF2alpha' vs 'wild type HIF2alpha'