Accession Number : ADA323916

Title :   Functions of Wild-Type and Mutant Forms of p53 in Breast Cancer.

Descriptive Note : Annual rept. 1 Aug 95-31 Jul 96,

Corporate Author : COLUMBIA UNIV NEW YORK

Personal Author(s) : Shieh, Sheau-Yannn ; Chen, Xinbin

PDF Url : ADA323916

Report Date : AUG 1996

Pagination or Media Count : 51

Abstract : It is well established that induction of the p53 tumor suppressor protein in cells can lead to either cell cycle arrest or apoptosis. To further understand features of p53 that contribute to these cell responses several p53-null Saos2 and H1299 cell lines were generated that express wild-type or mutant forms of p53, or the cyclin-dependent kinase inhibitor p21, under a tetracycline regulated promoter. Our results show that while the cellular level of p53 can dictate the response of the cell such that lower levels of p53 result in arrest while higher levels result in apoptosis, nevertheless DNA damage can heighten the apoptotic response to p53 without altering the protein level of p53 in cells. We also demonstrate that arrest and apoptosis are two genetically separable functions of p53 since a transcriptionally incompetent p53 can induce apoptosis but not arrest, while induction of p21, a transcriptional target of p53, can induce arrest but not apoptosis. Finally, we show that a full apoptotic response to p53 requires both its N- and C-termini, and our data suggest that there is synergistic cooperation between transcription-dependent and independent functions of p53 in apoptosis.

Descriptors :   *PROTEINS, *MUTATIONS, *BREAST CANCER, ENZYMES, NEOPLASMS, DEOXYRIBONUCLEIC ACIDS, RESPONSE(BIOLOGY), INHIBITORS, CELLS(BIOLOGY), GENETICS, CYCLIC COMPOUNDS, SYNERGISM, TETRACYCLINES, SUPPRESSORS, PHOSPHORUS TRANSFERASES.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE