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Complex functions of mutant p53 alleles from human prostate cancer
Author(s) -
Shi XuBao,
Nesslinger Nancy J.,
Deitch Arline D.,
Gumerlock Paul H.,
deVere White Ralph W.
Publication year - 2002
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10072
Subject(s) - allele , mutant , biology , null allele , transfection , prostate cancer , mutation , genetics , microbiology and biotechnology , cancer research , cancer , gene
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. Prostate 51:59–72, 2002. © 2002 Wiley‐Liss, Inc.