Role of Changes in the Expression of Cyclins and Retinoblastoma Protein in the Development of Breast Cancer
Abstract
Our studies, together with work carried out in other laboratories, have indicated that defects in the Rb-Cyclin D 1-p 16 cell cycle regulatory system are present in the vast majority of breast cancer cells. In previous years we have focused on characterizing these defects and on determining the mechanisms responsible for causing them. In the current year we have turned our efforts towards demonstrating the contribution of these defects to the tumorigenic properties of breast cancer cells, in order to provide potential targets for therapy. In particular, we have focused on the effects of restoring the expression of the tumor suppressor p16 in breast cancer cells, using constructs in which p16 expression in under control of the inducible Tet promoter. After demonstrating the feasibility of this approach in breast cancer cells in transiently transfected cells, we have now produced stably transfected ceU lines in order to test effects of p16 expression on growth in soft agar and in formation of tumors in nude mice. Currently we have demonstrated that MCF-7 breast cancer cells stably transformed with constructs expressing p16 are impaired or have lost the ability to grow in soft agar, indicating that defects in p16 expression may make a critical contribution to tumorigenicity. However, additional controls are required to establish unequivocally that loss of growth of these cells in soft agar is in fact due to restoration of p16 expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA368340
Entities
People
- Thomas Langan
Organizations
- University of Colorado Health