c- erb B-2 Related Aggressiveness in Breast Cancer Is Hypoxia Inducible Factor-1α Dependent
- 1 December 2004
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 10 (23), 7972-7977
- https://doi.org/10.1158/1078-0432.ccr-04-1068
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-1α (HIF1α) 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 HIF1α 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 HIF1α and CD31 endothelial cell antigen. c-erbB-2 positivity was clearly related to HIF1α protein expression and high angiogenesis. However, prognosis was decreased only in cases with simultaneous c-erbB-2 and HIF1α expression. If activation of c-erbB-2 in humans results in overexpression of HIF1α 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.Keywords
This publication has 28 references indexed in Scilit:
- Hypoxia-inducible factors 1?? and 2?? are related to vascular endothelial growth factor expression and a poorer prognosis in nodular malignant melanomas of the skinMelanoma Research, 2003
- Levels of hypoxia‐inducible factor‐1α independently predict prognosis in patients with lymph node negative breast carcinomaCancer, 2003
- Association of hypoxia‐inducible factors 1α and 2α with activated angiogenic pathways and prognosis in patients with endometrial carcinomaCancer, 2002
- Hypoxia — a key regulatory factor in tumour growthNature Reviews Cancer, 2002
- HER2 (neu) Signaling Increases the Rate of Hypoxia-Inducible Factor 1α (HIF-1α) Synthesis: Novel Mechanism for HIF-1-Mediated Vascular Endothelial Growth Factor ExpressionMolecular and Cellular Biology, 2001
- Hypoxia Response Elements in the Aldolase A, Enolase 1, and Lactate Dehydrogenase A Gene Promoters Contain Essential Binding Sites for Hypoxia-inducible Factor 1Journal of Biological Chemistry, 1996
- Hypoxic Regulation of Lactate Dehydrogenase AJournal of Biological Chemistry, 1995
- Inhibition of gap junctional intercellular communication and malignant transformation of rat liver epithelial cells by neu oncogeneCarcinogenesis: Integrative Cancer Research, 1995
- c-erbB-2 Gene Product Associates with Catenins in Human Cancer CellsBiochemical and Biophysical Research Communications, 1994
- The Product of the Human c- erb B-2 Gene: a 185-Kilodalton Glycoprotein with Tyrosine Kinase ActivityScience, 1986