MET and MYC cooperate in mammary tumorigenesis

Alana L. Welm, Suwon Kim, Bryan E. Welm, J. Michael Bishop

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

In human breast cancer, overexpression of the protooncogene MET is strongly associated with poor prognosis and high risk of metastasis. It stands out as a reliable prognostic indicator of survival and defines a set of tumors exclusive of those that express HER2 or hormone receptors. Studies have shown that overexpression of mutant forms of MET cause cancer in mice. However, MET mutations have not been found in human breast cancer, and the consequences of overexpression of normal MET are unknown. To investigate the role of MET and other putative oncogenes in breast cancer, we developed an experimental system that involves retroviral delivery of genes into primary mammary epithelial cells, followed by transplantation of the transduced cells into mammary fat pads. Using this approach, we found that overexpression of wild-type MET leads to the development of nonprogressive neoplasms. The lesions progressed to mammary adenocarcinoma when a second protooncogene, MYC, was overexpressed, indicating that MET and MYC cooperate in mammary tumorigenesis. Both the nonprogressive neoplasms and adenocarcinomas display characteristics consistent with transformation and expansion of mammary progenitor cells. The approach described here should provide a useful model with which to efficiently test effects of various genes on tumor development in the breast.

Original languageEnglish (US)
Pages (from-to)4324-4329
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number12
DOIs
StatePublished - Mar 22 2005
Externally publishedYes

Fingerprint

Carcinogenesis
Breast
Neoplasms
Breast Neoplasms
Adenocarcinoma
Cell Transplantation
Oncogenes
Genes
Adipose Tissue
Stem Cells
Epithelial Cells
Hormones
Neoplasm Metastasis
Mutation
Survival

Keywords

  • Breast cancer
  • Mouse models
  • Retrovirus

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

MET and MYC cooperate in mammary tumorigenesis. / Welm, Alana L.; Kim, Suwon; Welm, Bryan E.; Bishop, J. Michael.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 12, 22.03.2005, p. 4324-4329.

Research output: Contribution to journalArticle

Welm, Alana L. ; Kim, Suwon ; Welm, Bryan E. ; Bishop, J. Michael. / MET and MYC cooperate in mammary tumorigenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 12. pp. 4324-4329.
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