MYB Is Essential for Mammary Tumorigenesis

Rebecca Yu Miao, Yvette Drabsch, Ryan Stanley Cross, Dane Cheasley, Sandra Carpinteri, Lloyd Pereira, Jordane Malaterre, Thomas J. Gonda, Robin L. Anderson, Robert G. Ramsay*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

MYB oncogene upregulation is associated with estrogen receptor (ER)-positive breast cancer, but disease requirements for MYB function in vivo have not been explored. In this study, we provide evidence of a critical requirement for MYB functions in models of human and murine breast cancer. In human breast cancer, we found that MYB expression was critical for tumor cell growth both in vitro and in vivo in xenograft settings. In transgenic knockout mice, tissue-specific deletion of the murine MYB gene caused a transient defect in mammary gland development that was reflected in delayed ductal branching and defective apical bud formation. In mouse mammary tumor virus (MMTV)-NEU mice where tumors are initiated by activation of HER2, MYB deletion was sufficient to abolish tumor formation. In the more aggressive MMTV-PyMT model system, MYB deletion delayed tumorigenesis significantly. Together, the findings in these transgenic knockout models implied that MYB was critical during an early window in mammary development when it was essential for tumor initiation, even though MYB loss did not exert a lasting impact upon normal mammary function. Two important MYB-target genes that promote cell survival, BCL2 and GRP78/BIP, were each elevated compared with nontransformed mammary epithelial cells, thereby promoting survival as confirmed in colony formation assays in vitro. Taken together, our findings establish a role for MYB at the hub of ER-and HER2-dependent pathways in mammary carcinogenesis. Cancer Res; 71(22); 7029-37. (C)2011 AACR.

Original languageEnglish
Pages (from-to)7029-7037
Number of pages9
JournalCancer Research
Volume71
Issue number22
DOIs
Publication statusPublished - 15 Nov 2011

Keywords / Materials (for Non-textual outputs)

  • BREAST-CANCER CELLS
  • C-MYB
  • METASTATIC-DISEASE
  • TRANSGENIC MICE
  • COLONIC CRYPTS
  • MESSENGER-RNA
  • MOUSE MODEL
  • EXPRESSION
  • TRANSCRIPTION
  • GENE

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