| 1. |
- Hedberg, Y, et al.
(författare)
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Cyclin D3 protein content in human renal cell carcinoma in relation to cyclin D1 and clinico-pathological parameters
- 2002
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:2, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Aberrations in the G1/S checkpoint are common in malignancies and are probably important for tumor development. Few G1/S studies have been performed on renal cell carcinoma (RCC) and therefore in this study the cyclin D3 protein content in 80 RCCs and that in 12 corresponding normal kidney cortex tissues are characterized using Western blotting. High cyclin D3 protein content was observed in 16% of the tumors and was significantly associated with aneuploidy, high TNM stage, high nuclear grade, high proliferation and young age. There was no association between tumor cyclin D3 and patient survival. The cyclin D3 overexpression was confirmed by immunohistochemical staining of 72 tumors, showing both nuclear and cytoplasmic localization of cyclin D3 in a fraction of the tumors. The cyclin D1 content has earlier been characterized in this tumor material and there was no relation between cyclin D1 and cyclin D3 protein expression. In summary, a fraction of the tumors overexpressed cyclin D3, supporting that various aberrations in the G1/S transition are implicated in RCCs.
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| 2. |
- Hedberg, Y, et al.
(författare)
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Cyclin E and P27 protein content in human renal cell carcinoma: Clinical outcome and associations with cyclin D
- 2002
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 102:6, s. 601-607
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Tidskriftsartikel (refereegranskat)abstract
- Aberrations in the GI-S transition have been observed in several malignancies, suggesting that cell cycle defects are linked to the activation of oncogenes and inactivation of suppressor genes involved in the transformation process. The frequency of GI/S aberrations in human renal cell carcinoma (RCC) has not been fully clarified. We have therefore analyzed the cyclin E content, using Western blotting, in 79 RCC and 12 corresponding kidney cortex tissues as well as the fraction of p27-positive cells in 73 RCCs, using immunohistochemistry. Most of the tumors (65%) exhibited higher cyclin E levels than corresponding normal kidney cortex tissues. However, only a small fraction of the tumors (3 of 80) had excessive levels of cyclin E when cyclin E levels were compared with proliferation. Cyclin E levels higher than the median value were associated with aneuploicly (p = 0.025), high stage (p = 0.027), high grade (p = 0.013) and high erythrocyte sedimentation rate (ESR; p = 0.005). Cyclin E was further inversely correlated with cyclin D1 (p = 0.023) and positively correlated with cyclin D3 (p = 0.003). Most tumors (76%) demonstrated a normal fraction of p27-positive cells. There was an inverse correlation between p27 positivity and tumor size (p = 0.007), despite a lack of correlation between p27 and proliferation. Patients with p27 low tumors had a poor survival (p = 0.002). There was no correlation between p27 and cyclin E levels. In summary, the results suggest that protein expression of cyclin E and/or p27 is linked to tumor behavior. (C) 2002 Wiley-Liss, Inc.
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| 3. |
- Loden, M, et al.
(författare)
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The cyclin D1 high and cyclin E high subgroups of breast cancer: separate pathways in tumorogenesis based on pattern of genetic aberrations and inactivation of the pRb node
- 2002
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 21:30, s. 4680-4690
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Tidskriftsartikel (refereegranskat)abstract
- In an attempt to identify subtypes of breast cancer and pinpoint patterns of cell cycle regulatory defects associated with clinical behaviour, proliferation and other transformation associated events, a multitude of cell cycle regulatory proteins were analysed in a material of 113 primary breast cancers. Increased proliferation was observed in two different scenarios; (1) with high cyclin D1 and elevated retinoblastoma protein (pRb) phosphorylation, (cyclin D1(high) tumours) or (2) with high cyclin E protein but low cyclin D1 and lack of corresponding pRb phosphorylation (cyclin E high tumours) indicative of an interrupted pRb pathway. Characteristic for cyclin E-high tumours were further defects in p53, p27 and bcl-2, while c-erbB2 overexpression and c-myc amplification was found in both cyclin D1(high) and E-high tumours. Using transfected cell lines overexpressing cyclin E, cyclin E-high and D1(high) tumours were mimicked and the cyclin D1(high) cell line normalized the cyclin E kinase activity by an induction and redirection of p21 and p27 to the cyclin E complex whereas cyclin E-high cell lines obtained increased kinase activity with out redirection or inhibitors. Based on differences in genetic aberrations as well as function of the pRb node we therefore propose a model in which cyclin D1(high) and cyclin E-high tumours represent two alternative mechanisms to inactivate the pRb pathway and thereby achieve unrestrained growth in the tumorogenesis of breast cancer.
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