Evidence that p53-mediated cell-cycle-arrest inhibits chemotherapeutic treatment of ovarian carcinomas.

Autor: Carlos S Moreno, Lilya Matyunina, Erin B Dickerson, Nina Schubert, Nathan J Bowen, Sanjay Logani, Benedict B Benigno, John F McDonald
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Zdroj: PLoS ONE, Vol 2, Iss 5, p e441 (2007)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0000441
Popis: Gene expression profiles of malignant tumors surgically removed from ovarian cancer patients pre-treated with chemotherapy (neo-adjuvant) prior to surgery group into two distinct clusters. One group clusters with carcinomas from patients not pre-treated with chemotherapy prior to surgery (C-L), while the other clusters with non-malignant adenomas (A-L). We show here that although the C-L cluster is preferentially associated with p53 loss-of-function (LOF) mutations, the C-L cluster cancer patients display a more favorable clinical response to chemotherapy as evidenced by enhanced long-term survivorships. Our results support a model whereby p53 mediated cell-cycle-arrest/DNA repair serves as a barrier to optimal chemotherapeutic treatment of ovarian and perhaps other carcinomas and suggest that inhibition of p53 during chemotherapy may enhance clinical outcome.
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