P73 functionally replaces p53 in Adriamycin-treated, p53-deficient breast cancer cells
Authors: Laetitia Faridoni-Laurens
Jean Bénard
Muriel Vayssade
Sophie Tourpin
Jean-Charles Ahomadegbe
Hedi Haddada
Alexandre Valent
Journal: International Journal of Cancer (2005)
Discipline: CLINICAL MEDICINE
Keywords: p53-related genes; p73; p63; breast cancer; chemotherapy
Affiliations: Unité de Génétique Tumorale, Département de Biologie Clinique, Institut Gustave Roussy, Villejuif Cédex, France.

Abstract:  p53-Related genes, p73 and p63, encode 2 classes of proteins, TA-p73/p63 and DeltaN-p73/p63. TA-p73/p63 demonstrate p53-like properties including gene transactivation and cell death promotion, whereas DeltaN-p73/p63 lack these p53-like functions. Although p53-deficient cancer cells are often less responsive to chemotherapy, they are not completely drug resistant, suggesting that other apoptotic pathways are at work. Here, we compared for the first time to our knowledge p73 and p63 activation in various breast cancer (BC) cell lines after Adriamycin (ADR) treatment, an agent considered as mandatory in breast cancer chemotherapy. Our study was carried out using 1 p53-proficient BC cell line (MCF7 cells) and 3 BC cell lines deficient in p53 response (MCF7/ADR(IGR), MDA-MB157 and T47D) after ADR-induced genotoxic stress. We report that in cells with no p53 response after ADR treatment, TAp73, but not TAp63 or DeltaN-p73/p63, may replace p53 in triggering not only apoptosis but also cell cycle arrest or DNA repair effectors such as p21, GADD45, 14-3-3sigma and p53R2. We also demonstrate that TAp73 siRNA inhibits the accumulation of TAp73 in response to ADR treatment in MDA-MB157 cells and confers protection against ADR. ADR-induced downregulation of the DeltaNp73 isoform in the T47D cell line with nonfunctional mutant p53 further supports anti-apoptotic function of the isoform antagonistic to both p53 and TA-p73/p63. Exogenous TAp73 and DeltaNp73 overexpression in p53-response-deficient cell lines further confirms these results. cDNA microarray techniques demonstrated that the cellular response induced by p73 during ADR treatment could involve specific genes. 

Retracted: No

PubPeer comments:
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 2020 correction. https: doi.org 10.1002 ijc.33037 u201cP73 functionally replaces p53 in Adriamycinu2010treated, p53u2010deficient breast cancer cells.u201d Vayssade M, Haddada H, Faridoniu2010Laurens L, Tourpin S, Valent A, Bu00e9nard J, Ahomadegbe JC. Int J Cancer, 2005, 116(6):860u20109; https: doi.org 10.1002 ijc.21033 An Erratum is issued in relation to the above article, published online on April 22, 2005 in Wiley InterScience (www.interscience.wiley.com) and in volume 116, pp. 860u2010869, by agreement between the authors, the journal Editoru2010inu2010Chief, Prof. Christoph Plass and John Wiley Sons Ltd. The Erratum has been rendered due to concerns about the Western Blot in Figure 7. Through image integrity analysis it is presumed that individual bands in the left panel (MCF7 ADRIGR) of Figure 7, might have been improperly cut and pasted together in such a way that comparison to other bands, particular to controls, could be invalid: in the first row (Tap73u03b1, u0394u039dp73u03b1), between the third and fourth lane and in the third row (GADD45), also between the third and fourth lane. The authors are unable to retrieve the original data due to the time that has elapsed but believe that the concerns do not affect the data interpretation and overall conclusion of the paper. Given that the experiments presented in this manuscript have been performed in 2004 or earlier and experimental and logistic conditions are very different now, the editors consider that a reu2010performance of the experiments would not be appropriate. ,