title: Hypoxia inducible factor-alpha activation in lymphoma and relationship to the thioredoxin family.
abstract: Hypoxia inducible factors (HIFs) activate oncogenic pathways, while thioredoxins (Trx), including Trx1 and Trx reductases-1 and -2 (TrxR1 and TrxR2), promote HIF-alpha stabilization. In immunoblotting studies in lymphoma cell lines we found that Raji and SUDHL4 cells exhibited normoxic HIF-2alpha protein stabilization. Five cell lines showed increased TrxR1 expression, while only Namalwa, HF1 and SUDHL4 had Trx1 and TrxR2 activation. Tissue microarrays in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) identified different HIF expression among histological subgroups (e.g. 44% DLBCL vs. 11% of FL cases with moderate-to-high expression of HIF-1alpha and HIF-2alpha, P = 0.0017). These data demonstrate that HIF and the thioredoxin family are abnormally activated in lymphoma.
authors.affiliation: Lymphoma Program, Division of Hematology-Oncology, and Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USA. a-evens@northwestern.edu
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Evens
authors.forename: Paul T
authors.initials: PT
authors.lastname: Schumacker
authors.forename: Irene B
authors.initials: IB
authors.lastname: Helenowski
authors.forename: Amareshwar T K
authors.initials: AT
authors.lastname: Singh
authors.forename: Danijela
authors.initials: D
authors.lastname: Dokic
authors.forename: Anjeni
authors.initials: A
authors.lastname: Keswani
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kordeluk
authors.forename: Adekunle
authors.initials: A
authors.lastname: Raji
authors.forename: Jane N
authors.initials: JN
authors.lastname: Winter
authors.forename: Borko D
authors.initials: BD
authors.lastname: Jovanovic
authors.forename: Arne
authors.initials: A
authors.lastname: Holmgren
authors.forename: Beverly P
authors.initials: BP
authors.lastname: Nelson
authors.forename: Leo I
authors.initials: LI
authors.lastname: Gordon
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008223:Lymphoma / Q000378:metabolism*; D008224:Lymphoma, Follicular / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D013879:Thioredoxins / Q000502:physiology*; D014407:Tumor Cells, Cultured; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D013879:Thioredoxins; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human