Complex functions of mutant p53 alleles from human prostate cancer

Xu Bao Shi, Nancy J. Nesslinger, Arline D. Deitch, Paul H. Gumerlock, Ralph W deVere White

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)59-72
Number of pages14
JournalProstate
Volume51
Issue number1
DOIs
StatePublished - Apr 1 2002

Fingerprint

Prostatic Neoplasms
Alleles
Null Lymphocytes
Proliferating Cell Nuclear Antigen
S Phase
Agar
Interleukin-6
Cell Cycle
Up-Regulation
Yeasts
Mutation

Keywords

  • Dominant-negative
  • Gain-of-function
  • Loss-of-function
  • P53
  • Prostate cancer

ASJC Scopus subject areas

  • Urology

Cite this

Shi, X. B., Nesslinger, N. J., Deitch, A. D., Gumerlock, P. H., & deVere White, R. W. (2002). Complex functions of mutant p53 alleles from human prostate cancer. Prostate, 51(1), 59-72. https://doi.org/10.1002/pros.10072

Complex functions of mutant p53 alleles from human prostate cancer. / Shi, Xu Bao; Nesslinger, Nancy J.; Deitch, Arline D.; Gumerlock, Paul H.; deVere White, Ralph W.

In: Prostate, Vol. 51, No. 1, 01.04.2002, p. 59-72.

Research output: Contribution to journalArticle

Shi, XB, Nesslinger, NJ, Deitch, AD, Gumerlock, PH & deVere White, RW 2002, 'Complex functions of mutant p53 alleles from human prostate cancer', Prostate, vol. 51, no. 1, pp. 59-72. https://doi.org/10.1002/pros.10072
Shi, Xu Bao ; Nesslinger, Nancy J. ; Deitch, Arline D. ; Gumerlock, Paul H. ; deVere White, Ralph W. / Complex functions of mutant p53 alleles from human prostate cancer. In: Prostate. 2002 ; Vol. 51, No. 1. pp. 59-72.
@article{4f12747cff2544f7a601c4bf86248ced,
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.",
keywords = "Dominant-negative, Gain-of-function, Loss-of-function, P53, Prostate cancer",
author = "Shi, {Xu Bao} and Nesslinger, {Nancy J.} and Deitch, {Arline D.} and Gumerlock, {Paul H.} and {deVere White}, {Ralph W}",
year = "2002",
month = "4",
day = "1",
doi = "10.1002/pros.10072",
language = "English (US)",
volume = "51",
pages = "59--72",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Complex functions of mutant p53 alleles from human prostate cancer

AU - Shi, Xu Bao

AU - Nesslinger, Nancy J.

AU - Deitch, Arline D.

AU - Gumerlock, Paul H.

AU - deVere White, Ralph W

PY - 2002/4/1

Y1 - 2002/4/1

N2 - 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.

AB - 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.

KW - Dominant-negative

KW - Gain-of-function

KW - Loss-of-function

KW - P53

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=0036535482&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036535482&partnerID=8YFLogxK

U2 - 10.1002/pros.10072

DO - 10.1002/pros.10072

M3 - Article

VL - 51

SP - 59

EP - 72

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 1

ER -