Expression of p53-family members and associated target molecules in breast cancer cell lines in response to vincristine treatment.
As the antimitotic agent vincristine (VCR) has been reported to induce a weak p53 response in some studies, we hypothesised that p73 and p63, the recently described p53 homologues, may replace p53 in triggering apoptosis or cell cycle arrest effectors in VCR-treated cell lines. To address this issue, we measured p53, p73 and p63 mRNA and protein levels in two VCR-treated breast cancer cell lines, one p53-proficient (MCF7) and the other p53-deficient (MDA-MB157). We found an increase of p53 mRNA and protein levels in VCR-treated MCF7 cells, while, as expected, no p53 protein was detected in VCR-treated MDA-MB157 cells. Surprisingly, the p73 mRNA and protein expression levels decreased in both cell lines during VCR treatment, whereas p63 protein levels remained unchanged. In both cell lines, up-regulations of the canonical p53-target genes, such as p21 and GADD45, were consistently observed. We conclude that, in response to VCR treatment: (1) p53 is markedly induced in MCF7 cells, with the same extent than after DNA damaging drugs treatments; and (2) p63 is not involved, while p73 expression is down-regulated regardless of the p53 status of the cell lines. Our results therefore suggest the involvement of a fourth member of the p53 gene family, or the use of another pathway able to trigger canonical p53-target genes in response to VCR in p53-deficient cells.
Vayssade
Muriel
M
Unité des Marqueurs Génétiques des Cancers, Département de Biologie Clinique, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif, France.
Faridoni-Laurens
Laetitia
L
Bénard
Jean
J
Ahomadegbe
Jean Charles
JC
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D008565:Membrane Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation; D014750:Vincristine / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D014750:Vincristine