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

Hedberg, Y; Ljungberg, B; Roos, G and Landberg, Göran LU (2004) In International Journal of Cancer 109(2). p.189-193
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... (More)
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 ppRb(ser807/811) 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. (C) 2003 Wiley-Liss, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
renal cell carcinoma, GI/S-cyclins, cell cycle, retinoblastoma protein, phosphorylation
in
International Journal of Cancer
volume
109
issue
2
pages
189 - 193
publisher
John Wiley & Sons
external identifiers
  • wos:000189020300006
  • pmid:14750168
  • scopus:1242342071
ISSN
0020-7136
DOI
10.1002/ijc.11665
language
English
LU publication?
yes
id
d45c093e-3548-4a3b-9098-9cbd42684774 (old id 287108)
date added to LUP
2007-10-29 15:59:40
date last changed
2017-01-01 04:28:21
@article{d45c093e-3548-4a3b-9098-9cbd42684774,
  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 ppRb(ser807/811) 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. (C) 2003 Wiley-Liss, Inc.},
  author       = {Hedberg, Y and Ljungberg, B and Roos, G and Landberg, Göran},
  issn         = {0020-7136},
  keyword      = {renal cell carcinoma,GI/S-cyclins,cell cycle,retinoblastoma protein,phosphorylation},
  language     = {eng},
  number       = {2},
  pages        = {189--193},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Retinoblastoma protein in human renal cell carcinoma in relation to alterations in G1/S regulatory proteins},
  url          = {http://dx.doi.org/10.1002/ijc.11665},
  volume       = {109},
  year         = {2004},
}