JOURNAL ARTICLE

Role of AP-1 and HIF-1 transcription factors in TGF-beta activation of VEGF expression

S C Shih, K P Claffey
Growth Factors 2001, 19 (1): 19-34
11678207
Aberrant expression of vascular endothelial growth factor (VEGF) has been demonstrated to be associated with most human solid tumors. Here we report that TGF-beta potently induces VEGF expression in human HT-1080 fibrosarcomas primarily through transcriptional activation with no significant changes in mRNA turnover. The tyrosine kinase inhibitor genistein and AP-1 inhibitor curcumin significantly blocked TGF-beta induction of VEGF expression while SP-1 and MKK1 inhibitors did not. TGF-beta enhanced both AP-1 and HIF-1 DNA binding activities whereas SP-1, AP-2 and NF-1 did not show major changes. Transcriptional reporter assays provided further evidence that TGF-beta augmented both AP-1 and HIF-1 activities. Moreover, TGF-beta-treated HT-1080 cells contained higher levels of HIF-1alpha and c-jun proteins in nuclear extracts. TGF-beta and hypoxia synergistically induced VEGF mRNA expression. Given the fact that most tumors respond to hypoxic stress with increased VEGF expression via HIF-1-dependent transcription, this study identifies for the first time that TGF-beta also increases VEGF mRNA in an AP-l/HIF-1-dependent mechanism and may potentiate the hypoxic response.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
11678207
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"