Change search
ReferencesLink to record
Permanent link

Direct link
Hypoxia-inducible factor-1α mRNA and protein levels in renal cell carcinoma and in relation to kidney cortex tissue
Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
Show others and affiliations
Manuscript (Other academic)
URN: urn:nbn:se:umu:diva-2841OAI: diva2:141140
Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2010-01-13Bibliographically 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.
Umeå University medical dissertations, ISSN 0346-6612 ; 1141
renal cell carcinoma, hypoxia, RT-PCR, angiogenesis, western blot, tissue microarray, protein, mRNA, HIF-1 alpha, GLUT-1, survival
National Category
Urology and Nephrology
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)
Available from: 2007-12-05 Created: 2007-12-05 Last updated: 2009-09-22Bibliographically approved

Open Access in DiVA

No full text

By organisation
Surgical and Perioperative Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 19 hits
ReferencesLink to record
Permanent link

Direct link