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The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer
INTRODUCTION: Loss of the retinoblastoma protein tumor suppressor gene (RB) coding for a nuclear phosphoprotein that regulates the cell cycle is found in many human cancers and probably leads to disruption of the p16-cyclin D1-CDK4/6-RB pathway. Cyclin D1 is known to activate CDK4, which then phosph...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672746/ https://www.ncbi.nlm.nih.gov/pubmed/23336272 http://dx.doi.org/10.1186/bcr3376 |
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author | Peurala, Emmi Koivunen, Peppi Haapasaari, Kirsi-Maria Bloigu, Risto Jukkola-Vuorinen, Arja |
author_facet | Peurala, Emmi Koivunen, Peppi Haapasaari, Kirsi-Maria Bloigu, Risto Jukkola-Vuorinen, Arja |
author_sort | Peurala, Emmi |
collection | PubMed |
description | INTRODUCTION: Loss of the retinoblastoma protein tumor suppressor gene (RB) coding for a nuclear phosphoprotein that regulates the cell cycle is found in many human cancers and probably leads to disruption of the p16-cyclin D1-CDK4/6-RB pathway. Cyclin D1 is known to activate CDK4, which then phosphorylates the RB protein, leading to cell cycle progression. p16 inhibits CDK4, keeping RB hypophosphorylated and preventing cell cycle progression. The significance of these three markers, cyclin D1, CDK4 and p16, for breast cancer and carcinogenesis is nevertheless still controversial. METHODS: The material consisted of 102 formalin-fixed human breast cancer samples, in which cyclin D1, CDK4 and p16 expression was evaluated immunohistochemically. The amounts of cyclin D1 mRNA present were analyzed by quantitative real time PCR. RESULTS: High cyclin D1 expression statistically significantly correlated with lower tumor grade, estrogen and progesterone receptor positivity and lower proliferation activity in breast tumors and increased breast cancer-specific survival and overall survival. Tumors with high cyclin D1 protein had 1.8 times higher expression of cyclin D1 mRNA. CDK4 expression did not correlate with cyclin D1 expression or the survival data. p16 expression was associated with Human Epidermal Growth Factor Receptor 2 (HER2) negativity and increased breast cancer-specific survival and disease-free survival. No statistical correlations between cyclin D1, CDK4 and p16 were found. CONCLUSIONS: Cyclin D1 was associated with a good breast cancer prognosis but functioned independently of CDK4. High cyclin D1 expression may be partially due to increased CCND1 transcription. p16 correlated with a better prognosis and may function without CDK4. In conclusion, it appears that cyclin D1, CDK4 and p16 function independently in human breast cancer. |
format | Online Article Text |
id | pubmed-3672746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36727462013-06-06 The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer Peurala, Emmi Koivunen, Peppi Haapasaari, Kirsi-Maria Bloigu, Risto Jukkola-Vuorinen, Arja Breast Cancer Res Research Article INTRODUCTION: Loss of the retinoblastoma protein tumor suppressor gene (RB) coding for a nuclear phosphoprotein that regulates the cell cycle is found in many human cancers and probably leads to disruption of the p16-cyclin D1-CDK4/6-RB pathway. Cyclin D1 is known to activate CDK4, which then phosphorylates the RB protein, leading to cell cycle progression. p16 inhibits CDK4, keeping RB hypophosphorylated and preventing cell cycle progression. The significance of these three markers, cyclin D1, CDK4 and p16, for breast cancer and carcinogenesis is nevertheless still controversial. METHODS: The material consisted of 102 formalin-fixed human breast cancer samples, in which cyclin D1, CDK4 and p16 expression was evaluated immunohistochemically. The amounts of cyclin D1 mRNA present were analyzed by quantitative real time PCR. RESULTS: High cyclin D1 expression statistically significantly correlated with lower tumor grade, estrogen and progesterone receptor positivity and lower proliferation activity in breast tumors and increased breast cancer-specific survival and overall survival. Tumors with high cyclin D1 protein had 1.8 times higher expression of cyclin D1 mRNA. CDK4 expression did not correlate with cyclin D1 expression or the survival data. p16 expression was associated with Human Epidermal Growth Factor Receptor 2 (HER2) negativity and increased breast cancer-specific survival and disease-free survival. No statistical correlations between cyclin D1, CDK4 and p16 were found. CONCLUSIONS: Cyclin D1 was associated with a good breast cancer prognosis but functioned independently of CDK4. High cyclin D1 expression may be partially due to increased CCND1 transcription. p16 correlated with a better prognosis and may function without CDK4. In conclusion, it appears that cyclin D1, CDK4 and p16 function independently in human breast cancer. BioMed Central 2013 2013-01-21 /pmc/articles/PMC3672746/ /pubmed/23336272 http://dx.doi.org/10.1186/bcr3376 Text en Copyright © 2013 Peurala et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Peurala, Emmi Koivunen, Peppi Haapasaari, Kirsi-Maria Bloigu, Risto Jukkola-Vuorinen, Arja The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer |
title | The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer |
title_full | The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer |
title_fullStr | The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer |
title_full_unstemmed | The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer |
title_short | The prognostic significance and value of cyclin D1, CDK4 and p16 in human breast cancer |
title_sort | prognostic significance and value of cyclin d1, cdk4 and p16 in human breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672746/ https://www.ncbi.nlm.nih.gov/pubmed/23336272 http://dx.doi.org/10.1186/bcr3376 |
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