Identification of p53 and Its Isoforms in Human Breast Carcinoma Cells

In breast carcinoma, disruption of the p53 pathway is one of the most common genetic alterations. The observation that the p53 can express multiple protein isoforms adds a novel level of complexity to the outcome of p53 mutations. p53 expression was analysed by Western immunoblotting and immunohisto...

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Main Authors: Zorka Milićević, Vladan Bajić, Lada Živković, Jelena Kasapović, Uroš Andjelković, Biljana Spremo-Potparević
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1155/2014/618698
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author Zorka Milićević
Vladan Bajić
Lada Živković
Jelena Kasapović
Uroš Andjelković
Biljana Spremo-Potparević
author_facet Zorka Milićević
Vladan Bajić
Lada Živković
Jelena Kasapović
Uroš Andjelković
Biljana Spremo-Potparević
author_sort Zorka Milićević
collection DOAJ
description In breast carcinoma, disruption of the p53 pathway is one of the most common genetic alterations. The observation that the p53 can express multiple protein isoforms adds a novel level of complexity to the outcome of p53 mutations. p53 expression was analysed by Western immunoblotting and immunohistochemistry using monoclonal antibodies DO-7, Pab240, and polyclonal antiserum CM-1. The more frequently p53-positive nuclear staining has been found in the invasive breast tumors. One of the most intriguing findings is that mutant p53 appears as discrete dot-shaped regions within the nucleus of breast cancer cells. In many malignant cells, the nucleolar sequestration of p53 is evident. These observations support the view that the nucleolus is involved directly in the mediation of p53 function or indirectly by the control of the localization of p53 interplayers. p53 expressed in the nuclear fraction of breast cancer cells revealed a wide spectrum of isoforms. p53 isoforms ΔNp53 (47 kDa) and Δ133p53β (35 kDa), known as dominant-negative repressors of p53 function, were detected as the most predominant variants in nuclei of invasive breast carcinoma cells. The isoforms expressed also varied between individual tumors, indicating potential roles of these p53 variants in human breast cancer.
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spelling doaj-art-6048fca83a02459690c5ddccccf5ee452025-02-03T01:00:00ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/618698618698Identification of p53 and Its Isoforms in Human Breast Carcinoma CellsZorka Milićević0Vladan Bajić1Lada Živković2Jelena Kasapović3Uroš Andjelković4Biljana Spremo-Potparević5Laboratory of Molecular Biology and Endocrinology, “Vinča” Institute of Nuclear Sciences, University of Belgrade, Mihaila Petrovića Alasa 12-14, P.O. Box 522, 11 001 Belgrade, SerbiaBiomedical Department, Institute for Pharmaceutical Research and Development, Galenika a.d., Pasterova 2, 11 000 Belgrade, SerbiaDepartment of Biology and Human Genetics, Institute of Physiology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11 000 Belgrade, SerbiaLaboratory of Molecular Biology and Endocrinology, “Vinča” Institute of Nuclear Sciences, University of Belgrade, Mihaila Petrovića Alasa 12-14, P.O. Box 522, 11 001 Belgrade, SerbiaDepartment of Chemistry, Institute for Chemistry, Technology and Metallurgy, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, SerbiaDepartment of Biology and Human Genetics, Institute of Physiology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11 000 Belgrade, SerbiaIn breast carcinoma, disruption of the p53 pathway is one of the most common genetic alterations. The observation that the p53 can express multiple protein isoforms adds a novel level of complexity to the outcome of p53 mutations. p53 expression was analysed by Western immunoblotting and immunohistochemistry using monoclonal antibodies DO-7, Pab240, and polyclonal antiserum CM-1. The more frequently p53-positive nuclear staining has been found in the invasive breast tumors. One of the most intriguing findings is that mutant p53 appears as discrete dot-shaped regions within the nucleus of breast cancer cells. In many malignant cells, the nucleolar sequestration of p53 is evident. These observations support the view that the nucleolus is involved directly in the mediation of p53 function or indirectly by the control of the localization of p53 interplayers. p53 expressed in the nuclear fraction of breast cancer cells revealed a wide spectrum of isoforms. p53 isoforms ΔNp53 (47 kDa) and Δ133p53β (35 kDa), known as dominant-negative repressors of p53 function, were detected as the most predominant variants in nuclei of invasive breast carcinoma cells. The isoforms expressed also varied between individual tumors, indicating potential roles of these p53 variants in human breast cancer.http://dx.doi.org/10.1155/2014/618698
spellingShingle Zorka Milićević
Vladan Bajić
Lada Živković
Jelena Kasapović
Uroš Andjelković
Biljana Spremo-Potparević
Identification of p53 and Its Isoforms in Human Breast Carcinoma Cells
The Scientific World Journal
title Identification of p53 and Its Isoforms in Human Breast Carcinoma Cells
title_full Identification of p53 and Its Isoforms in Human Breast Carcinoma Cells
title_fullStr Identification of p53 and Its Isoforms in Human Breast Carcinoma Cells
title_full_unstemmed Identification of p53 and Its Isoforms in Human Breast Carcinoma Cells
title_short Identification of p53 and Its Isoforms in Human Breast Carcinoma Cells
title_sort identification of p53 and its isoforms in human breast carcinoma cells
url http://dx.doi.org/10.1155/2014/618698
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