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The expression of hypoxia-inducible factor 1alpha is a favorable independent prognostic factor in renal cell carcinoma
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology. Urologi och andrologi.
Umeå University, Faculty of Medicine, Medical Biosciences. Umeå University, Faculty of Medicine, Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Biomedical Laboratory Science.
Umeå University, Faculty of Medicine, Medical Biosciences, Clinical chemistry. Klinisk kemi.
Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Onkologi.
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2005 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 11, no 3, 1129-1135 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2005. Vol. 11, no 3, 1129-1135 p.
Identifiers
URN: urn:nbn:se:umu:diva-14449PubMedID: 15709180OAI: oai:DiVA.org:umu-14449DiVA: diva2:154120
Available from: 2007-09-14 Created: 2007-09-14 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Hypoxia inducible factor-1α in renal cell carcinoma
Open this publication in new window or tab >>Hypoxia inducible factor-1α in renal cell carcinoma
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hypoxia Inducible Factor-1α in Renal Cell Carcinoma

Departments of Surgical and Perioperative Sciences, Urology and Andrology; Radiation Sciences, Oncology; Medical Biosciences, Pathology; and Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden

Background: Renal cell carcinoma (RCC) accounts for approximately 2-3% of all human cancers. A distinguished feature of RCC is vascularisation and among the three dominating RCC types conventional RCC (cRCC) generally is more vascularised than papillary RCC (pRCC) and chromophobe RCC (chRCC). Angiogenesis is a critical step in tumour progression controlled by a balance involving molecules that have positive and negative regulatory activity. A balance distorted by metabolic stress such as hypoxia, acidosis, and inflammation. Hypoxia-Inducible Factor 1α (HIF-1α) is a key transcription factor in angiogenesis and tumour progression, targeting more than a 100 genes involved in vascular growth and regulation, iron metabolism and erythropoesis, collagen matrix formation, regulation of extracellular pH, glucose uptake and metabolism, proliferation, apoptosis, differentiation, and cell viability.

Methods: Tumour tissue and corresponding kidney cortex from nephrectomised RCC patients was used in order to characterize HIF-1α expression and one of its target genes, Glucose Transporter 1 (GLUT-1). All tumour samples were thoroughly described regarding tumour type, TNM stage, nuclear grade, tumour size, vein invasion, and patient survival. Utilizing RT-PCR, Westen Blot and Tissue micro array (TMA) we studied HIF-1α mRNA and protein expression as well as GLUT-1 protein expression, correlating them to each other and clinicopathological parameters.

Results: Using Western Blot, HIF-1α protein expression differed significantly between the different RCC types and kidney cortex. In cRCC, high expression of HIF-1α was an independent prognostic factor for favourable prognosis.

TMA is a useful method to analyze HIF-1α protein expression in RCC. HIF-1α levels were significantly lower in locally aggressive cRCC and patients with high levels of HIF-1 tended to have a better prognosis.

GLUT-1 levels were higher in cRCC than in other RCC types and for cRCC a correlation to HIF-1α was seen.

HIF-1α mRNA levels were significantly lower in cRCC compared to other RCC types and kidney cortex. An inverse correlation between HIF-1α protein expression and mRNA levels was observed.

Summary: These results demonstrate a discrepancy between RCC types, highlighting the need to separately evaluate biological events in different RCC types. Overexpression of HIF-1α protein is not necessarily all bad and translational regulation appears more critical than anticipated. Further studies are encouraged to clarify angiogenic pathways in RCC.

Place, publisher, year, edition, pages
Umeå: Kirurgisk och perioperativ vetenskap, 2007. 60 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1141
Keyword
renal cell carcinoma, hypoxia, RT-PCR, angiogenesis, western blot, tissue microarray, protein, mRNA, HIF-1 alpha, GLUT-1, survival
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:umu:diva-1462 (URN)978-91-7264-452-6 (ISBN)
Public defence
2007-12-21, Betula, 6M, NUS, Umeå, 09:00 (English)
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Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2009-09-22Bibliographically approved

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