title: Complex functions of mutant p53 alleles from human prostate cancer.
abstract: BACKGROUND
  Few studies have used multiple assays to examine the functionality of mutant p53 in prostate cancer (CaP). We employed seven functional assays to study 16 representative mutant p53 alleles, six from localized and ten from metastatic CaP.
  
  
  METHODS
  Yeast assays were employed to determine loss of function (LOF), partial function (PF), and dominant-negative status. Assays using p53-null Saos2 cells were used to determine whether mammalian cells transfected with mutant p53 could up-regulate the MDR-1 or PCNA promoters, alter IL-6 expression or confer the ability to grow in soft agar. As a further test of gain of function (GOF), p53-null PC3 cells stably transfected with these mutant p53 alleles were examined for cell cycle distributions.
  
  
  RESULTS
  All 16 mutant p53 alleles demonstrated either total or partial LOF. All but one allele also had at least one gain of function; however, the pattern of GOF was different for each mutant allele. Alleles derived from both localized and metastatic CaP had similar GOF characteristics; however, only alleles from metastatic disease had significantly increased S-phase fractions.
  
  
  CONCLUSIONS
  Different mutant p53 alleles from CaP had different, complex functional profiles. The lack of predictable patterns for these alleles suggest that each mutation may uniquely affect p53 function.
authors.affiliation: Department of Urology, University of California, Davis, School of Medicine, Sacramento, California 95817, USA.
authors.forename: Xu-Bao
authors.initials: XB
authors.lastname: Shi
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Nesslinger
authors.forename: Arline D
authors.initials: AD
authors.lastname: Deitch
authors.forename: Paul H
authors.initials: PH
authors.lastname: Gumerlock
authors.forename: Ralph W
authors.initials: RW
authors.lastname: deVere White
mesh_terms: D000483:Alleles; D015153:Blotting, Western; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005434:Flow Cytometry; D016158:Genes, p53 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D016297:Mutagenesis, Site-Directed; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016196:S Phase / Q000502:physiology; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins