Apc mutation enhances PyMT-induced mammary tumorigenesis.

The Adenomatous Polyposis Coli (APC) tumor suppressor gene is silenced by hypermethylation or mutated in up to 70% of human breast cancers. In mouse models, Apc mutation disrupts normal mammary development and predisposes to mammary tumor formation; however, the cooperation between APC and other mut...

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Autores principales:	Jenifer R Prosperi, Andrey I Khramtsov, Galina F Khramtsova, Kathleen H Goss
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1a508e31c7274de4b7bff2af4c2a70e5
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spelling	oai:doaj.org-article:1a508e31c7274de4b7bff2af4c2a70e52021-11-18T07:31:35ZApc mutation enhances PyMT-induced mammary tumorigenesis.1932-620310.1371/journal.pone.0029339https://doaj.org/article/1a508e31c7274de4b7bff2af4c2a70e52011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22216254/?tool=EBIhttps://doaj.org/toc/1932-6203The Adenomatous Polyposis Coli (APC) tumor suppressor gene is silenced by hypermethylation or mutated in up to 70% of human breast cancers. In mouse models, Apc mutation disrupts normal mammary development and predisposes to mammary tumor formation; however, the cooperation between APC and other mutations in breast tumorigenesis has not been studied. To test the hypothesis that loss of one copy of APC promotes oncogene-mediated mammary tumorigenesis, Apc(Min/+) mice were crossed with the mouse mammary tumor virus (MMTV)-Polyoma virus middle T antigen (PyMT) or MMTV-c-Neu transgenic mice. In the PyMT tumor model, the Apc(Min/+) mutation significantly decreased survival and tumor latency, promoted a squamous adenocarcinoma phenotype, and enhanced tumor cell proliferation. In tumor-derived cell lines, the proliferative advantage was a result of increased FAK, Src and JNK signaling. These effects were specific to the PyMT model, as no changes were observed in MMTV-c-Neu mice carrying the Apc(Min/+) mutation. Our data indicate that heterozygosity of Apc enhances tumor development in an oncogene-specific manner, providing evidence that APC-dependent pathways may be valuable therapeutic targets in breast cancer. Moreover, these preclinical model systems offer a platform for dissection of the molecular mechanisms by which APC mutation enhances breast carcinogenesis, such as altered FAK/Src/JNK signaling.Jenifer R ProsperiAndrey I KhramtsovGalina F KhramtsovaKathleen H GossPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e29339 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jenifer R Prosperi Andrey I Khramtsov Galina F Khramtsova Kathleen H Goss Apc mutation enhances PyMT-induced mammary tumorigenesis.
description	The Adenomatous Polyposis Coli (APC) tumor suppressor gene is silenced by hypermethylation or mutated in up to 70% of human breast cancers. In mouse models, Apc mutation disrupts normal mammary development and predisposes to mammary tumor formation; however, the cooperation between APC and other mutations in breast tumorigenesis has not been studied. To test the hypothesis that loss of one copy of APC promotes oncogene-mediated mammary tumorigenesis, Apc(Min/+) mice were crossed with the mouse mammary tumor virus (MMTV)-Polyoma virus middle T antigen (PyMT) or MMTV-c-Neu transgenic mice. In the PyMT tumor model, the Apc(Min/+) mutation significantly decreased survival and tumor latency, promoted a squamous adenocarcinoma phenotype, and enhanced tumor cell proliferation. In tumor-derived cell lines, the proliferative advantage was a result of increased FAK, Src and JNK signaling. These effects were specific to the PyMT model, as no changes were observed in MMTV-c-Neu mice carrying the Apc(Min/+) mutation. Our data indicate that heterozygosity of Apc enhances tumor development in an oncogene-specific manner, providing evidence that APC-dependent pathways may be valuable therapeutic targets in breast cancer. Moreover, these preclinical model systems offer a platform for dissection of the molecular mechanisms by which APC mutation enhances breast carcinogenesis, such as altered FAK/Src/JNK signaling.
format	article
author	Jenifer R Prosperi Andrey I Khramtsov Galina F Khramtsova Kathleen H Goss
author_facet	Jenifer R Prosperi Andrey I Khramtsov Galina F Khramtsova Kathleen H Goss
author_sort	Jenifer R Prosperi
title	Apc mutation enhances PyMT-induced mammary tumorigenesis.
title_short	Apc mutation enhances PyMT-induced mammary tumorigenesis.
title_full	Apc mutation enhances PyMT-induced mammary tumorigenesis.
title_fullStr	Apc mutation enhances PyMT-induced mammary tumorigenesis.
title_full_unstemmed	Apc mutation enhances PyMT-induced mammary tumorigenesis.
title_sort	apc mutation enhances pymt-induced mammary tumorigenesis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/1a508e31c7274de4b7bff2af4c2a70e5
work_keys_str_mv	AT jeniferrprosperi apcmutationenhancespymtinducedmammarytumorigenesis AT andreyikhramtsov apcmutationenhancespymtinducedmammarytumorigenesis AT galinafkhramtsova apcmutationenhancespymtinducedmammarytumorigenesis AT kathleenhgoss apcmutationenhancespymtinducedmammarytumorigenesis
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Apc mutation enhances PyMT-induced mammary tumorigenesis.

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