Characterization of Two Novel Oncogenic Pathways Collaborating With Loss of p53 or Activated Neu in Mouse Models of Breast Cancer
Abstract
Cancer is a complex multi step disease and progresses through successive accumulation of genetic mutations. Loss of tumor suppressor gene p53 and activation of oncogene Neu/ErbB2 are among the most frequent genetic alterations in human breast cancer. We performed a retroviral insertional mutagenesis screen to identify gene 5 that my contribute to mammary tumor formation in conjunction with deregulated p53 or Neu. Multiple proviral insertions form independent tumors were identified to be located within introns of the F-Box gene Fbw4, suggesting that the structural alteration at this locus may provide selective growth advantage. The viral integrations result in marked overexpression of a novel Fbw4 short isoform, which is also spontaneously enriched in several mouse and human breast cancer cell lines and thus appears to be associated with tumor formation. Overexpression of this short isoform in the normal' mouse mammary epithelial cell line NMuMg enable these cells to grow in soft agar. Taken together, these findings suggest that Fbw4 in a novel cancer- relevant gene. We propose a mechanism related to Fbw4's oncogenic properties.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA423676
Entities
People
- Jiangrong Lu
- Philip Leder
Organizations
- Harvard Medical School