title: Inhibition of hypoxia inducible factor-2 transcription: isolation of active modulators from marine sponges.
abstract: Renal or kidney cancer accounts for about 3% of all cancer cases reported each year in the U.S. Molecular signatures that define the cancer, such as the loss of functional VHL, are found in both sporadic and familial cases of cancer. In clear cell renal cancer, the transcription factor HIF-2α has been shown to have a distinct role in tumorigenesis. Our laboratories developed a cell-based screen to identify modulators of HIF-2α. Screening of the NCI's Natural Product Extract Repository resulted in the identification of 10 sponge extracts, from which 12 compounds were isolated. The biological evaluation of these compounds will be discussed including evaluation of HIF-1α vs HIF-2α selectivity and the isolated compounds' effects on mRNA from several pathways regulated by HIF.
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA. mckeeta@mail.nih.gov
authors.forename: Tawnya C
authors.initials: TC
authors.lastname: McKee
authors.forename: Daniel
authors.initials: D
authors.lastname: Rabe
authors.forename: Heidi R
authors.initials: HR
authors.lastname: Bokesch
authors.forename: Tanja
authors.initials: T
authors.lastname: Grkovic
authors.forename: Emily L
authors.initials: EL
authors.lastname: Whitson
authors.forename: Thushara
authors.initials: T
authors.lastname: Diyabalanage
authors.forename: Albert W W
authors.initials: AW
authors.lastname: Van Wyk
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Marcum
authors.forename: Roberta S
authors.initials: RS
authors.lastname: Gardella
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Gustafson
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
authors.forename: James B
authors.initials: JB
authors.lastname: McMahon
authors.forename: Donald P
authors.initials: DP
authors.lastname: Bottaro
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism; D008386:Marine Biology; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001688:Biological Products; D012333:RNA, Messenger; D000099162:Endothelial PAS Domain-Containing Protein 1