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Cyclin D3 protein content in human renal cell carcinoma in relation to cyclin D1 and clinicopathological parameters.
Umeå University, Faculty of Medicine, Medical Biosciences.
2002 In: Acta Oncologica, ISSN 0284-186X, Vol. 41, no 2, 175-181 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2002. Vol. 41, no 2, 175-181 p.
URN: urn:nbn:se:umu:diva-4297OAI: diva2:143323
Available from: 2003-06-11 Created: 2003-06-11Bibliographically approved
In thesis
1. Cell Cycle Regulation in Human Renal Cell Carcinoma
Open this publication in new window or tab >>Cell Cycle Regulation in Human Renal Cell Carcinoma
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]


Cell cycle regulation in human renal cell carcinoma

Ylva Hedberg, Departments of Medical Biosciences, Pathology, and Surgical and

Perioperative Sciences, Urology Andrology, Umeå University, Sweden

Deregulated growth control is a hallmark of neoplasia potentially caused by aberrant expression of cell cycle regulatory proteins. The importance of such aberrations in human renal cell carcinoma (RCC) has not been fully clarified. Therefore, the protein expressions of several G1/S regulatory proteins in human RCC were evaluated and their relation to clinico-pathological data was examined.

Western blotting and immunohistochemistry were used to detect the proteinexpression of cyclin D1, D3, and E in 80 RCCs. Most tumors expressed higher levels of cyclin D1 (75%) and cyclin E (65%) compared to corresponding normal kidney cortex. In contrast, only 16 % of the tumors had high levels of cyclin D3. In conventional RCCs, low levels of cyclin D1 were associated with large tumor size, aneuploidy and a poor outcome for the patients. High expression of cyclin D3 and E

were associated with aneuploidy, high proliferation, high TNM-stage, and high nuclear grade. Cyclin E was positively correlated to cyclin D3 but inversely associated with cyclin D1. Cyclin D3 and E were not associated with survival. The majority of RCCs had normal p27 levels, determined by immunohistochemistry, whereas the few tumors with low p27 levels were associated with large tumor size and poor survival.

In order to confirm and extend our initial studies, a tissue microarray consisting of 218 RCCs was constructed and cyclin D1, D3, E, p27 were detected by immunohistochemistry. The tissue microarray results were validated by comparing the array data with western analyzes. Due to the large number of tumors analyzed we could evaluate potential differences in expression patterns of cell cycle regulators between conventional, papillary, and chromophobe RCCs. Interestingly, the protein expression differed between RCC types, showing that the conventional tumors generally had high cyclin D1 expression. In contrast, papillary and chromophobe RCCs had high cyclin E expression. Downregulation of p27 was found mostly in chromophobe RCCs.

The retinoblastoma protein (pRb) was detected in all RCCs. Phosphorylation of pRb, detected by western blotting or immunohistochemistry and phospho-specific antibodies, was observed in approximately 50% of the tumors. The cdk-inhibitor p16 was not overexpressed suggesting that pRb was functional in the majority of RCCs.

In summary, abnormal expression of G1-cyclins and the CDK-inhibitor p27 was common in RCC whereas the main G1/S-substrate, pRb, seemed to be functional. The aberrations further differed between the separate RCC subtypes and were linked to clinical behavior.

48 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 839
Medicine, Human Renal Cell Carcinoma, Cell Cycle, G1/S, Protein, Cyclin, p27, pRb, Phosphorylation, Tissue Microarray, Clinical Behaviour, Medicin
National Category
Dermatology and Venereal Diseases
Research subject
Medical Cell Biology
urn:nbn:se:umu:diva-38 (URN)91-7305-445-3 (ISBN)
Public defence
2003-05-30, Hörsal Betula, Byggnad M6, Umeå, 09:00
Available from: 2003-06-11 Created: 2003-06-11Bibliographically approved

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