title: c-erbB-2 related aggressiveness in breast cancer is hypoxia inducible factor-1alpha dependent.
abstract: c-erbB-2-positive breast carcinomas are highly aggressive tumors. In vitro data on breast cell lines showed that c-erbB-2 enhanced translational efficiency of hypoxia inducible factor-1alpha (HIF1alpha) production (Laughner et al., Mol Cell Biol 2001;21:3995-4005). We investigated the clinical correlate of this observation to assess whether c-erbB-2 expression was related to HIF1alpha expression, angiogenesis, and prognosis. A series of 180 breast carcinomas of known c-erbB-2 status (90 c-erbB-2-positive and 90 c-erbB-2-negative carcinomas) were stained immunohistochemically for HIF1alpha and CD31 endothelial cell antigen. c-erbB-2 positivity was clearly related to HIF1alpha protein expression and high angiogenesis. However, prognosis was decreased only in cases with simultaneous c-erbB-2 and HIF1alpha expression. If activation of c-erbB-2 in humans results in overexpression of HIF1alpha independently of conditions of hypoxia, as occur in experimental studies, this interaction may represent a main pathway conferring clinical aggressiveness to c-erbB-2-positive breast tumors.
authors.affiliation: Department of Pathology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.g.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: Michael I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: Costantinos
authors.initials: C
authors.lastname: Simopoulos
authors.forename: Alexandros
authors.initials: A
authors.lastname: Polychronidis
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Gatter
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: Efthimios
authors.initials: E
authors.lastname: Sivridis
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D004730:Endothelium, Vascular; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D000080864:Lactate Dehydrogenase 5; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014157:Transcription Factors; C497442:HIF1A protein, human