The Role of B-Myb in Human Breast Cancer Progression
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: The Myb protein family is important for normal chromosome biology because proteins that contain Myb domains play essential roles in telomere and centromere maintenance, nucleosome assembly (DNA packaging) and remodeling, and histone modification. Recent clinical studies by others have shown that B-MYB is one of a small number of genes that are sufficient to predict disease recurrence in tamoxifen-treated node-negative breast cancer patients. Thus, B-MYB was selected by Genomic Health, Inc. (Redwood City) as one of 21 genes used in its proprietary Oncotype DX™ assay. Recent work in our own laboratory has shown that Drosophila (fruit fly) Myb is required for controlling chromosome number (ploidy) and that vertebrate B-MYB (but not other MYB genes) can function in place of Drosophila Myb. In addition, recent studies from two other laboratories have shown that the Drosophila Myb protein is present in a large complex that also contains the E2F and RB protein products, the human homologues of which are implicated in the progression of human breast cancer.
 
 
 
 
 
 
 
 We hypothesize that elevated levels of B-MYB are predictive of failures of treatment response because elevated levels of B-MYB are permissive for the generation of and required for the maintenance of aneuploidy (i.e., additions or deletions of a small number of whole chromosomes) in breast cancer cells. We have now proposed experiments to directly test this hypothesis. In addition, we will generate antibodies against human B-MYB to be used in histochemical studies to determine whether B-MYB protein levels are a better and/or less expensive way of predicting outcome in human breast cancer. Our specific aims are:
 
 (1) to generate matched human benign and malignant mammary epithelial cell lines that differ only in levels of B-MYB protein in order to determine effects on chromosome number, cell growth rates, differentiation, and invasion during sequential passage;
 
 (2) to produce a panel of polyclonal antisera directed against different regions of the human B-MYB protein and to compare immunostaining with in situ hybridization (e.g. FISH assays) for predictive value in breast cancer progression.
 
 
 
 
 
 
 
 For the first specific aim we will initially use established human mammary cell lines that are phenotypically normal and have been well characterized for the properties of interest (e.g., MCF-10 derivatives). Retroviral cDNA transduction will be used to increase B-MYB levels; retroviral RNAi transduction will be used to decrease B-MYB levels. For the second specific aim we will immunize rabbits with proteins. B-MYB antisera will be tested by immunoblotting in our laboratory and on breast tissue microarravs in the laboratory of Matt van de Rijn at Stanford. 
 
 
 
 
 
 
 
 Key issues in human breast cancer include improved early diagnosis, better predictors of which patients will (or will not) benefit from aggressive and often debilitating therapy, and development of targeted therapies with decreased toxicity. B-MYB is one of a small number of genes that are sufficient to predict the recurrence of disease following initial treatment. The utility of B-MYB in breast cancer diagnosis has recently been demonstrated using a proprietary assay. We believe that the development of B-MYB antibodies for immunostaining may lead to a better and cheaper test. In addition, our studies of B-MYB function may lead to the development of new targeted therapies for breast cancer.