Adenovirus-mediated TA-p73beta gene transfer increases chemosensitivity of human malignant melanomas

Apoptosis : an International Journal on Programmed Cell Death
S TuveB M Pützer

Abstract

Malignant melanoma is the most aggressive form of skin cancer and has proven to be highly resistant to conventional chemotherapy. Intriguingly, the p53 tumor suppressor, a main mediator of chemoresistance in other tumor types, is rarely mutated in melanoma. However, we have previously shown that anti-apoptotic isoforms of p73 (deltaTA-p73), another member of the p53 family, are overexpressed in metastatic melanomas. DeltaTA-p73 can oppose the pro-apoptotic functions of p53 and full length p73, and thus it could contribute to melanoma chemoresistance. In this study, we use an efficient adenoviral-based gene transfer approach to introduce a transcriptionally active form of p73 (TA-p73beta) in melanoma cells, with the objective of overcoming drug resistance. Interestingly, TA-p73beta significantly sensitized 5 out of 7 aggressive melanoma cell lines to the standard therapeutic agents adriamycin and cisplatin. More importantly, TA-p73beta displayed a synergistic effect in vivo allowing adriamycin or cisplatin to block melanoma cell growth in mouse xenograft models (p < 0.05). In summary, our data show that Ad-mediated TA-p73beta gene expression can markedly sensitize a subset of melanoma cell lines to adriamycin and cisplatin in vi...Continue Reading

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Citations

Apr 11, 2008·Apoptosis : an International Journal on Programmed Cell Death·Guo-Rui RuanXiao-Jun Huang
Jun 25, 2009·Apoptosis : an International Journal on Programmed Cell Death·Min XieGuo-Rui Ruan
Aug 24, 2011·Apoptosis : an International Journal on Programmed Cell Death·Francesca Nicolau-GalmésMaría D Boyano
Apr 18, 2013·Cancer Metastasis Reviews·Stella LogothetiVassilis Zoumpourlis
Feb 20, 2013·The Journal of Experimental Medicine·Rubeta N MatinDaniele Bergamaschi
Jul 20, 2007·Blood·Arnon P KaterThomas J Kipps
Feb 28, 2008·Biochimica Et Biophysica Acta·Sven Buhlmann, Brigitte M Pützer
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May 10, 2007·Journal of Cellular and Molecular Medicine·B M Pützer
Mar 15, 2006·Trends in Molecular Medicine·Jens Stanelle, Brigitte M Pützer
Jul 6, 2012·Bioscience Reports·Dulcie LaiXiaolong Yang
Sep 11, 2021·Cell Biology International·Larissa J SanchesAlessandra L Cecchini

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