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Hypoxia-inducible f...
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Helczynska, KarolinaLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
(författare)
Hypoxia-inducible factor-2alpha correlates to distant recurrence and poor outcome in invasive breast cancer.
- Artikel/kapitelEngelska2008
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LIBRIS-ID:oai:lup.lub.lu.se:9c788ac0-2b96-4196-9c41-9ba11d8475e7
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https://lup.lub.lu.se/record/1271428URI
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https://doi.org/10.1158/0008-5472.CAN-08-1135DOI
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Språk:engelska
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Sammanfattning på:engelska
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Differential regulation as well as target gene specificity of the two hypoxia-inducible factor (HIF)-alpha subunits HIF-1alpha and HIF-2alpha in various tumors and cell lines have been suggested. In breast cancer, the prognostic significance of HIF-1alpha is not clear-cut and that of HIF-2alpha is largely unknown. Using IHC analyses of HIF-1alpha, HIF-2alpha, and vascular endothelial growth factor (VEGF) expression in a tissue microarray of invasive breast cancer specimens from 512 patients, we investigated the expression patterns of the 2 HIF-alpha subunits in relation to established clinicopathologic variables, VEGF expression, and survival. HIF-1alpha and HIF-2alpha protein levels and their effect on survival were additionally analyzed in a second cohort of 179 patients. To evaluate the individual role of each subunit in the hypoxic response and induction of VEGF, HIF-alpha protein and HIF-alpha and VEGF mRNA levels were further studied in cultured breast cancer cells after hypoxic induction and/or knockdown of HIF-alpha subunits by siRNA by Western blot and Quantitative Real-Time PCR techniques. We showed that although HIF-1alpha and HIF-2alpha protein levels in breast cancer specimens were not interrelated, high levels of both HIF-1alpha and HIF-2alpha associated to high VEGF expression. HIF-2alpha expression was an independent prognostic factor associated to reduced recurrence-free and breast cancer-specific survival, whereas HIF-1alpha did not exhibit these correlations. In cultured cells, acute hypoxia induced both HIF-proteins. At prolonged hypoxia, HIF-2alpha remained accumulated, whereas HIF-1alpha protein levels decreased, in agreement with the oxygen level and time-dependent induction of HIFs recently reported in neuroblastoma.
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Larsson, Anna-MariaLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine(Swepub:lu)onk-aol
(författare)
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Holmquist Mengelbier, LindaLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine(Swepub:lu)molm-lho
(författare)
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Bridges Baxter, EstherLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine(Swepub:lu)med-ber
(författare)
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Fredlund, ErikLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine(Swepub:lu)molm-efr
(författare)
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Borgquist, SigneLund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups(Swepub:lu)ront-sbo
(författare)
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Landberg, GöranLund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups(Swepub:lu)pat-gla
(författare)
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Påhlman, SvenLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine(Swepub:lu)molm-spa
(författare)
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Jirström, KarinLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pat-kji
(författare)
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Institutionen för translationell medicinMedicinska fakulteten
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Cancer Research68:22, s. 9212-92201538-7445
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