Potential tumor suppressor role for the c-Myb oncogene in luminal breast cancer.
BACKGROUND
The transcription factor c-Myb has been well characterized as an oncogene in several human tumor types, and its expression in the hematopoietic stem/progenitor cell population is essential for proper hematopoiesis. However, the role of c-Myb in mammopoeisis and breast tumorigenesis is poorly understood, despite its high expression in the majority of breast cancer cases (60-80%).


RESULTS
We find that c-Myb high expression in human breast tumors correlates with the luminal/ER+ phenotype and a good prognosis. Stable RNAi knock-down of endogenous c-Myb in the MCF7 luminal breast tumor cell line increased tumorigenesis both in vitro and in vivo, suggesting a possible tumor suppressor role in luminal breast cancer. We created a mammary-derived c-Myb expression signature, comprised of both direct and indirect c-Myb target genes, and found it to be highly correlated with a published mature luminal mammary cell signature and least correlated with a mammary stem/progenitor lineage gene signature.


CONCLUSIONS
These data describe, for the first time, a possible tumor suppressor role for the c-Myb proto-oncogene in breast cancer that has implications for the understanding of luminal tumorigenesis and for guiding treatment.
Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
Aaron R
AR
Thorner
Joel S
JS
Parker
Katherine A
KA
Hoadley
Charles M
CM
Perou
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019070:Cell Lineage; D005260:Female; D055785:Gene Knockdown Techniques; D016147:Genes, Tumor Suppressor; D006801:Humans; D009857:Oncogenes; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*; D034622:RNA Interference
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb