Neoplastic Consequences of a Mutator Phenotype in Human Breast Epithelial Cells: A Prospective Analysis
Abstract
Overexpression of DNA polymerase beta in the breast epithelial cell line, MCF-lOA, resulted in loss of proliferative potential, most probably due to the upregulation of pro- apoptotic proteins, such as Hax. The ras-transformed MCF-1OAT cell line is more tolerant of pol-beta overexpression, possibly due to the increased levels of Bcl-2 protein in these cells. However, the MCP-lOAT cells continue to display a progressive loss of proliferative potential resulting from pol-beta overexpression. We observed an alteration in MCF-lCAT cell phenotype from an adherent to a floating cell morphology after pol-beta overexpression. This is a novel observation and may be related to underlying genomic changes resulting from increased pol-beta protein levels. MCFlOAT cells overexpressing poln displayed a tumor incidence and latency similar to parental cells. Thus, in contrast to what we observe in cell culture, a subpopulation of pol-beta overexpressing cells retains proliferative potential in vivo. We hypothesize that biologic selection occurs for a mutant, MCE-l0AT/WTpol-beta cell variant within the mouse environment. The requisite genetic variation may be related to the adherent to floating morphology change. The observations that the MCF-lOAT/pol-beta tumors are sac-like rather than solid, and that animals bearing MCF-lOAT/pol-beta tumors progressed to form lung metastases, further supports our hypothesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA408674
Entities
People
- Danny R. Welch
- Kristin A. Eckert
Organizations
- Penn State College of Medicine