Mutation or loss of p53 differentially modifies TGFβ action in ovarian cancer.

Ovarian cancer is the most lethal gynecological disease affecting women in the US. The Cancer Genome Atlas Network identified p53 mutations in 96% of high-grade serous ovarian carcinomas, demonstrating its critical role. Additionally, the Transforming Growth Factor Beta (TGFβ) pathway is dysfunction...

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Autores principales:	Eoghainín Ó hAinmhire, Suzanne M Quartuccio, Whay Cheng, Roshan A Ahmed, Shelby M King, Joanna E Burdette
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f96d07137ceb4af39b4e4d5c53e1082f
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spelling	oai:doaj.org-article:f96d07137ceb4af39b4e4d5c53e1082f2021-11-18T08:31:40ZMutation or loss of p53 differentially modifies TGFβ action in ovarian cancer.1932-620310.1371/journal.pone.0089553https://doaj.org/article/f96d07137ceb4af39b4e4d5c53e1082f2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24586866/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Ovarian cancer is the most lethal gynecological disease affecting women in the US. The Cancer Genome Atlas Network identified p53 mutations in 96% of high-grade serous ovarian carcinomas, demonstrating its critical role. Additionally, the Transforming Growth Factor Beta (TGFβ) pathway is dysfunctional in various malignancies, including ovarian cancer. This study investigated how expression of wild-type, mutant, or the absence of p53 alters ovarian cancer cell response to TGFβ signaling, as well as the response of the ovarian surface epithelium and the fallopian tube epithelium to TGFβ. Only ovarian cancer cells expressing wild-type p53 were growth inhibited by TGFβ, while ovarian cancer cells that were mutant or null p53 were not. TGFβ induced migration in p53 null SKOV3 cells, which was not observed in SKOV3 cells with stable expression of mutant p53 R273H. Knockdown of wild-type p53 in the OVCA 420 ovarian cancer cells enhanced cell migration in response to TGFβ. Increased protein expression of DKK1 and TMEPAI, two pro-invasive genes with enhanced expression in late stage metastatic ovarian cancer, was observed in p53 knockdown and null cells, while cells stably expressing mutant p53 demonstrated lower DKK1 and TMEPAI induction. Expression of mutant p53 or loss of p53 permit continued proliferation of ovarian cancer cell lines in the presence of TGFβ; however, cells expressing mutant p53 exhibit reduced migration and decreased protein levels of DKK1 and TMEPAI.Eoghainín Ó hAinmhireSuzanne M QuartuccioWhay ChengRoshan A AhmedShelby M KingJoanna E BurdettePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89553 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eoghainín Ó hAinmhire Suzanne M Quartuccio Whay Cheng Roshan A Ahmed Shelby M King Joanna E Burdette Mutation or loss of p53 differentially modifies TGFβ action in ovarian cancer.
description	Ovarian cancer is the most lethal gynecological disease affecting women in the US. The Cancer Genome Atlas Network identified p53 mutations in 96% of high-grade serous ovarian carcinomas, demonstrating its critical role. Additionally, the Transforming Growth Factor Beta (TGFβ) pathway is dysfunctional in various malignancies, including ovarian cancer. This study investigated how expression of wild-type, mutant, or the absence of p53 alters ovarian cancer cell response to TGFβ signaling, as well as the response of the ovarian surface epithelium and the fallopian tube epithelium to TGFβ. Only ovarian cancer cells expressing wild-type p53 were growth inhibited by TGFβ, while ovarian cancer cells that were mutant or null p53 were not. TGFβ induced migration in p53 null SKOV3 cells, which was not observed in SKOV3 cells with stable expression of mutant p53 R273H. Knockdown of wild-type p53 in the OVCA 420 ovarian cancer cells enhanced cell migration in response to TGFβ. Increased protein expression of DKK1 and TMEPAI, two pro-invasive genes with enhanced expression in late stage metastatic ovarian cancer, was observed in p53 knockdown and null cells, while cells stably expressing mutant p53 demonstrated lower DKK1 and TMEPAI induction. Expression of mutant p53 or loss of p53 permit continued proliferation of ovarian cancer cell lines in the presence of TGFβ; however, cells expressing mutant p53 exhibit reduced migration and decreased protein levels of DKK1 and TMEPAI.
format	article
author	Eoghainín Ó hAinmhire Suzanne M Quartuccio Whay Cheng Roshan A Ahmed Shelby M King Joanna E Burdette
author_facet	Eoghainín Ó hAinmhire Suzanne M Quartuccio Whay Cheng Roshan A Ahmed Shelby M King Joanna E Burdette
author_sort	Eoghainín Ó hAinmhire
title	Mutation or loss of p53 differentially modifies TGFβ action in ovarian cancer.
title_short	Mutation or loss of p53 differentially modifies TGFβ action in ovarian cancer.
title_full	Mutation or loss of p53 differentially modifies TGFβ action in ovarian cancer.
title_fullStr	Mutation or loss of p53 differentially modifies TGFβ action in ovarian cancer.
title_full_unstemmed	Mutation or loss of p53 differentially modifies TGFβ action in ovarian cancer.
title_sort	mutation or loss of p53 differentially modifies tgfβ action in ovarian cancer.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f96d07137ceb4af39b4e4d5c53e1082f
work_keys_str_mv	AT eoghaininohainmhire mutationorlossofp53differentiallymodifiestgfbactioninovariancancer AT suzannemquartuccio mutationorlossofp53differentiallymodifiestgfbactioninovariancancer AT whaycheng mutationorlossofp53differentiallymodifiestgfbactioninovariancancer AT roshanaahmed mutationorlossofp53differentiallymodifiestgfbactioninovariancancer AT shelbymking mutationorlossofp53differentiallymodifiestgfbactioninovariancancer AT joannaeburdette mutationorlossofp53differentiallymodifiestgfbactioninovariancancer
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Mutation or loss of p53 differentially modifies TGFβ action in ovarian cancer.

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