The Role of Chk1 Kinase in Cell Cycle Checkpoint Response in Breast Epithelial Cells
Abstract
P63 IS A RECENTLY IDENTIFIED HOMOLOG OF P53 THAT IS FOUND IN THE BASAL LAYER OF SEVERAL EPITHELIAL TISSUES SUCH AS THE EPIDERMIS, ORAL MUCOSA, PROSTATE, UROGENITAL TRACT, AND MAMMARY GLAND. Studies with p63-/- mice and analysis of several human autosomal dominant disorders with germline p63 mutations suggest p63 involvement in maintaining epithelial stem cell populations. However, the biochemical mechanisms by which p63 functions are not well understood. The objective of the current study is to determine the splice variants that are expressed in primary human mammary epithelial cells (HMECs) and the biochemical activity p63 has in these epithelial cell populations. Progress to date includes (i) cloning of p63 splice variants and development of assay systems in primary epidermal cell cultures to analyze p63 expression and biochemical activity; (ii) determining that p63 represses transcription and binds directly to p53 consensus sites in the p21 and 14-3-3 sigma promoters in vitro and in vitro; (iii) development of optimal growth conditions for primary human mammary epithelial cells. It is critical to obtain a more thorough understanding of how p63 works at the molecular level in HMECs to better understand the role of p63 in breast cancer development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA410123
Entities
People
- Jennifer A. Pietenpol
- Matthew D. Westfall
Organizations
- Vanderbilt University Medical Center