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Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
MYB is essential for mammary tumorigenesis
Rebecca Yu Miao1, Yvette Drabsch, Ryan Stanley Cross
1Peter MacCallum Cancer Centre and Department of Pathology, University of Melbourne, Melbourne, Victoria, Australia.
Cancer Research
|September 28, 2011
Summary
MYB oncogene is essential for breast cancer growth and initiation in both human and mouse models. Its deletion impacts mammary gland development and delays tumor formation, highlighting its role in carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MYB oncogene upregulation is linked to estrogen receptor (ER)-positive breast cancer.
- The in vivo requirement for MYB in breast cancer has not been fully elucidated.
- MYB plays a role in cell survival pathways.
Purpose of the Study:
- To investigate the critical requirement of MYB function in human and murine breast cancer models.
- To explore the role of MYB in mammary gland development and tumorigenesis.
- To identify MYB-target genes involved in cell survival.
Main Methods:
- Xenograft models of human breast cancer.
- Transgenic knockout mice with tissue-specific MYB deletion.
- Mouse Mammary Tumor Virus (MMTV)-NEU and MMTV-PyMT models.
- In vitro and in vivo assays including colony formation assays.
Main Results:
- MYB expression is critical for tumor cell growth in vitro and in vivo.
- MYB deletion in transgenic mice caused transient mammary gland development defects.
- MYB deletion abolished tumor formation in MMTV-NEU mice and delayed it in MMTV-PyMT mice.
- BCL2 and GRP78/BIP were identified as MYB-target genes promoting cell survival.
Conclusions:
- MYB is critical for breast cancer initiation and progression in both ER- and HER2-dependent pathways.
- MYB plays a crucial role during an early window of mammary development essential for tumor initiation.
- MYB regulates cell survival pathways, contributing to mammary carcinogenesis.
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