Identification of Novel Mitotic Checkpoint Genes in Breast Cancer
Abstract
Malignant progression in mammary epithelial cells stems from the accumulation of multiple mutations in tumor suppressor genes and protooncogenes. It is widely hypothesized that these mutations arise in part due to some degree of genomic instability. Given most breast cancer cells demonstrate some degree of aneuploidy suggesting chromosomal instability, we wanted to examine breast cancer cells for the relationship of chromosomal instability to alterations in genes and proteins that regulate the mitotic spindle checkpoint. We first characterized the degree of chromosomal instability in breast cancer cells and examined the cells for alterations in known spindle checkpoint genes (MAD2Ll, MAD1L1, BUBi, BUBRi, and CDC2O) and their related proteins. We then searched for novel proteins that interact with spindle checkpoint proteins and identified EBi. While few alterations were found in BUBi, BUBRi, EBi, and CDC2O, we found decreased transcript' and protein expression of MAD1L1 and MAD2L1 in breast cancer cells. Mutation analysis of these genes reveals some alterations that may drive malignant progression. Further in vitro and in vivo analyses are underway to characterize how alterations in spindle checkpoint genes may contribute to mammary carcinogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA408761
Entities
People
- Elizabeth M. Petty
Organizations
- University of Michigan