Apc mutation enhances pyMT-induced mammary tumorigenesis

Jenifer R. Prosperi, Andrey I. Khramtsov, Galina F. Khramtsova, Kathleen H. Goss

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere29339
JournalPLoS ONE
Volume6
Issue number12
DOIs
StatePublished - Dec 22 2011

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Adenomatous Polyposis Coli
Mouse mammary tumor virus
carcinogenesis
breasts
Tumors
Carcinogenesis
Breast
Polyomavirus
Viral Tumor Antigens
mutation
Mutation
Viruses
neoplasms
oncogenes
Breast Neoplasms
antigens
Oncogenes
breast neoplasms
viruses
Neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Prosperi, J. R., Khramtsov, A. I., Khramtsova, G. F., & Goss, K. H. (2011). Apc mutation enhances pyMT-induced mammary tumorigenesis. PLoS ONE, 6(12), [e29339]. https://doi.org/10.1371/journal.pone.0029339

Apc mutation enhances pyMT-induced mammary tumorigenesis. / Prosperi, Jenifer R.; Khramtsov, Andrey I.; Khramtsova, Galina F.; Goss, Kathleen H.

In: PLoS ONE, Vol. 6, No. 12, e29339, 22.12.2011.

Research output: Contribution to journalArticle

Prosperi, Jenifer R. ; Khramtsov, Andrey I. ; Khramtsova, Galina F. ; Goss, Kathleen H. / Apc mutation enhances pyMT-induced mammary tumorigenesis. In: PLoS ONE. 2011 ; Vol. 6, No. 12.
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