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Hypoxia-inducible factor 1alpha expression in renal cell carcinoma analyzed by tissue microarray
Umeå universitet, Medicinsk fakultet, Kirurgisk och perioperativ vetenskap, Urologi och andrologi. Urologi och andrologi.
Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap. Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi. Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi. Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Biomedicinsk laboratorievetenskap.
Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi. Klinisk kemi.
Umeå universitet, Medicinsk fakultet, Strålningsvetenskaper, Onkologi. Onkologi.
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2006 (Engelska)Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 50, nr 6, s. 1272-1277Artikel i tidskrift (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
2006. Vol. 50, nr 6, s. 1272-1277
Nyckelord [en]
Hypoxia-inducible factor, HIF-1alpha, RCC, prognosis, tissue microarray
Identifikatorer
URN: urn:nbn:se:umu:diva-15717DOI: doi:10.1016/j.eururo.2006.05.043PubMedID: 16814458OAI: oai:DiVA.org:umu-15717DiVA, id: diva2:155389
Tillgänglig från: 2007-09-14 Skapad: 2007-09-14 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ingår i avhandling
1. Hypoxia inducible factor-1α in renal cell carcinoma
Öppna denna publikation i ny flik eller fönster >>Hypoxia inducible factor-1α in renal cell carcinoma
2007 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Umeå: Kirurgisk och perioperativ vetenskap, 2007. s. 60
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1141
Nyckelord
renal cell carcinoma, hypoxia, RT-PCR, angiogenesis, western blot, tissue microarray, protein, mRNA, HIF-1 alpha, GLUT-1, survival
Nationell ämneskategori
Urologi och njurmedicin
Identifikatorer
urn:nbn:se:umu:diva-1462 (URN)978-91-7264-452-6 (ISBN)
Disputation
2007-12-21, Betula, 6M, NUS, Umeå, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2007-12-05 Skapad: 2007-12-05 Senast uppdaterad: 2009-09-22Bibliografiskt granskad

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Lidgren, AndersHedberg, YlvaGrankvist, KjellRasmuson, TorgnyBergh, AndersLjungberg, Börje

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Urologi och andrologiMedicinsk biovetenskapPatologiKlinisk mikrobiologiBiomedicinsk laboratorievetenskapKlinisk kemiOnkologi
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