Neoplastic Consequences of a Mutator Phenotype in Human Breast Epithelial Cells: A Prospective Analysis
Abstract
Non-tumorigenic MCF-10AT and tumorigenic MCF-10AT cells were stably transfected with pIRES-pol beta. DNA polymerase B overexpression in both cell lines resulted in loss of proliferative potential through apoptosis. Pol beta overexpression in MCF-10AT/AT cells increased the number of apoptotic cells within the population and altered the ratios of pro- and anti-apoptotic protein levels. Pol beta overexpression in MCF-10A cells resulted in a low incidence of tumors. Pol B overexpression in MCF-10A cells resulted in a reduced incidence relative the parental cells, but an increased incidence relative to the vector control cells. The suppression of MCF-10AT cell tumorigenicity in the vector transfected controls is likely due to the observed molecular alterations in cell cycle progression proteins induced by puromycin selection. The tumors produced by pol beta-overexpressing cells displayed an altered histology, relative to the MCF-10AT parental tumors. Molecular analysis of MCF-10A or AT/poIB tumors demonstrated that exogenous poIB protein expression was diminished or lost in the tumor population. We propose that poIB overexpression induces genomic instability in MCF-10A and MCF-10AT cells, resulting primarily in cell death. In rare cells, or within the host environment of the mammary fat pad, cells are selected that have extended proliferative potential, allowing for additional genetic changes and neoplastic progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA430121
Entities
People
- Kristin A. Eckert
Organizations
- Pennsylvania State University