Retinoblastoma protein in human renal cell carcinoma in relation to alterations in G1/S regulatory proteins

Ylva Hedberg, Börje Ljungberg, Göran Roos, Göran Landberg

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The retinoblastoma gene product (pRb) is the main substrate for cyclin-dependent kinases (CDKs) during the G1/S transition. Aberrations in cell cycle regulatory proteins, which have been observed in many malignancies, can theoretically cause increased phosphorylation of pRb due to unbalanced CDK activities. The expression and phosphorylation of pRb and potential associations to cell cycle aberrations in renal cell carcinomas (RCC) has only partly been clarified. We therefore evaluated the presence of pRb and the level of pRb-phosphorylation in 216 RCCs arranged in tissue microarrays by using different pRb-antibodies, including pRb-phosphospecific antibodies. Most RCCs (95%) expressed pRb, while cases with the low pRb levels, potentially indicative for pRb-inactivation, were few. In order to detect secondary alterations to a potential pRb-inactivation, the p 16 expression was also monitored. None of the tumors exhibited increased p 16 levels, confirming that pRb-inactivation is rare in RCC. Phosphorylated pRb was detected in approximately 50% of the RCCs, using Western blotting or immunohistochemistry. The immunohistochemical ppRbser807/811 levels were associated with high proliferation, cyclin D1, cyclin E and p27 protein content. Surprisingly, there was no association between pRb-phosphorylation and clinicopathological data. In summary, pRb seemed to be functional and aberrations in G1/ S-regulatory proteins were associated with increased phosphorylation of pRb and proliferation. The data supports that pRb might be one of the main cell cycle regulators in RCC. © 2003 Wiley-Liss, Inc.
    Original languageEnglish
    Pages (from-to)189-193
    Number of pages4
    JournalInternational Journal of Cancer
    Volume109
    Issue number2
    DOIs
    Publication statusPublished - 20 Mar 2004

    Keywords

    • Cell cycle
    • G1/S-cyclins
    • Phosphorylation
    • Renal cell carcinoma
    • Retinoblastoma protein

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