Frequent alteration of CDKN2 (p16(INK4A)/MTS1) expression in human primary prostate carcinomas

Sung Gil Chi, Ralph W deVere White, Jared T. Muenzer, Paul H. Gumerlock

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

CDKN2 (p16(INK4A)/MTS1) is found to be mutated in a variety of human tumor types. To explore the involvement of CDKN2 in prostate carcinogenesis, alterations of CDKN2 were examined in 116 human prostate tissues and cell lines and xenografts. Markedly reduced expression of CDKN2 mRNA was found in 43% (26 of 60) of untreated primary carcinomas, whereas no alteration was observed in 10 benign prostatic hyperplasias. In 17 matched sets from individual patients, 41% of cancerous tissues in contrast to 6% of noncancerous tissues expressed low levels of CDKN2 mRNA, supporting the role of CDKN2 as a tumor suppressor in prostate cancer. Alteration of CDKN2 was observed in each prostate tumor cell line, including one with a missense mutation, and in one of three xenograft tumor tissues derived from primary carcinomas. Two cell lines (PC-3 and TSU-Pr1) expressed only CDKN2 E1β transcripts, indicating that the expression of CDKN2 E1α and E1β are under separate control in the prostate. A high level of CDKN2 expression was related to abnormal RB1 in one primary tumor and in the DU145 cell line, which expressed the mutated CDKN2 allele. Analysis of genomic DNA indicated that altered CDKN2 expression in primary carcinomas of the prostate was more frequently due to down-regulation of transcription (five of seven) than deletion of the gene (two of seven). Additionally, CDKN2 mRNA was induced in nonexpressor cell lines by treatment with 5-aza-2'-deoxycytidine. This study demonstrates that alteration of CDKN2 is one of the most frequent genetic abnormalities in prostate cancer and may contribute to prostate carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1889-1897
Number of pages9
JournalClinical Cancer Research
Volume3
Issue number10
StatePublished - Oct 1997

Fingerprint

Cyclin-Dependent Kinase Inhibitor p16
Prostate
Carcinoma
Cell Line
decitabine
Heterografts
Messenger RNA
Neoplasms
Prostatic Neoplasms
Carcinogenesis
Gene Deletion
Prostatic Hyperplasia
Missense Mutation
Tumor Cell Line
Down-Regulation
Alleles
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Frequent alteration of CDKN2 (p16(INK4A)/MTS1) expression in human primary prostate carcinomas. / Chi, Sung Gil; deVere White, Ralph W; Muenzer, Jared T.; Gumerlock, Paul H.

In: Clinical Cancer Research, Vol. 3, No. 10, 10.1997, p. 1889-1897.

Research output: Contribution to journalArticle

Chi, Sung Gil ; deVere White, Ralph W ; Muenzer, Jared T. ; Gumerlock, Paul H. / Frequent alteration of CDKN2 (p16(INK4A)/MTS1) expression in human primary prostate carcinomas. In: Clinical Cancer Research. 1997 ; Vol. 3, No. 10. pp. 1889-1897.
@article{6980863b51244573aac5f9c3e5298274,
title = "Frequent alteration of CDKN2 (p16(INK4A)/MTS1) expression in human primary prostate carcinomas",
abstract = "CDKN2 (p16(INK4A)/MTS1) is found to be mutated in a variety of human tumor types. To explore the involvement of CDKN2 in prostate carcinogenesis, alterations of CDKN2 were examined in 116 human prostate tissues and cell lines and xenografts. Markedly reduced expression of CDKN2 mRNA was found in 43{\%} (26 of 60) of untreated primary carcinomas, whereas no alteration was observed in 10 benign prostatic hyperplasias. In 17 matched sets from individual patients, 41{\%} of cancerous tissues in contrast to 6{\%} of noncancerous tissues expressed low levels of CDKN2 mRNA, supporting the role of CDKN2 as a tumor suppressor in prostate cancer. Alteration of CDKN2 was observed in each prostate tumor cell line, including one with a missense mutation, and in one of three xenograft tumor tissues derived from primary carcinomas. Two cell lines (PC-3 and TSU-Pr1) expressed only CDKN2 E1β transcripts, indicating that the expression of CDKN2 E1α and E1β are under separate control in the prostate. A high level of CDKN2 expression was related to abnormal RB1 in one primary tumor and in the DU145 cell line, which expressed the mutated CDKN2 allele. Analysis of genomic DNA indicated that altered CDKN2 expression in primary carcinomas of the prostate was more frequently due to down-regulation of transcription (five of seven) than deletion of the gene (two of seven). Additionally, CDKN2 mRNA was induced in nonexpressor cell lines by treatment with 5-aza-2'-deoxycytidine. This study demonstrates that alteration of CDKN2 is one of the most frequent genetic abnormalities in prostate cancer and may contribute to prostate carcinogenesis.",
author = "Chi, {Sung Gil} and {deVere White}, {Ralph W} and Muenzer, {Jared T.} and Gumerlock, {Paul H.}",
year = "1997",
month = "10",
language = "English (US)",
volume = "3",
pages = "1889--1897",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "10",

}

TY - JOUR

T1 - Frequent alteration of CDKN2 (p16(INK4A)/MTS1) expression in human primary prostate carcinomas

AU - Chi, Sung Gil

AU - deVere White, Ralph W

AU - Muenzer, Jared T.

AU - Gumerlock, Paul H.

PY - 1997/10

Y1 - 1997/10

N2 - CDKN2 (p16(INK4A)/MTS1) is found to be mutated in a variety of human tumor types. To explore the involvement of CDKN2 in prostate carcinogenesis, alterations of CDKN2 were examined in 116 human prostate tissues and cell lines and xenografts. Markedly reduced expression of CDKN2 mRNA was found in 43% (26 of 60) of untreated primary carcinomas, whereas no alteration was observed in 10 benign prostatic hyperplasias. In 17 matched sets from individual patients, 41% of cancerous tissues in contrast to 6% of noncancerous tissues expressed low levels of CDKN2 mRNA, supporting the role of CDKN2 as a tumor suppressor in prostate cancer. Alteration of CDKN2 was observed in each prostate tumor cell line, including one with a missense mutation, and in one of three xenograft tumor tissues derived from primary carcinomas. Two cell lines (PC-3 and TSU-Pr1) expressed only CDKN2 E1β transcripts, indicating that the expression of CDKN2 E1α and E1β are under separate control in the prostate. A high level of CDKN2 expression was related to abnormal RB1 in one primary tumor and in the DU145 cell line, which expressed the mutated CDKN2 allele. Analysis of genomic DNA indicated that altered CDKN2 expression in primary carcinomas of the prostate was more frequently due to down-regulation of transcription (five of seven) than deletion of the gene (two of seven). Additionally, CDKN2 mRNA was induced in nonexpressor cell lines by treatment with 5-aza-2'-deoxycytidine. This study demonstrates that alteration of CDKN2 is one of the most frequent genetic abnormalities in prostate cancer and may contribute to prostate carcinogenesis.

AB - CDKN2 (p16(INK4A)/MTS1) is found to be mutated in a variety of human tumor types. To explore the involvement of CDKN2 in prostate carcinogenesis, alterations of CDKN2 were examined in 116 human prostate tissues and cell lines and xenografts. Markedly reduced expression of CDKN2 mRNA was found in 43% (26 of 60) of untreated primary carcinomas, whereas no alteration was observed in 10 benign prostatic hyperplasias. In 17 matched sets from individual patients, 41% of cancerous tissues in contrast to 6% of noncancerous tissues expressed low levels of CDKN2 mRNA, supporting the role of CDKN2 as a tumor suppressor in prostate cancer. Alteration of CDKN2 was observed in each prostate tumor cell line, including one with a missense mutation, and in one of three xenograft tumor tissues derived from primary carcinomas. Two cell lines (PC-3 and TSU-Pr1) expressed only CDKN2 E1β transcripts, indicating that the expression of CDKN2 E1α and E1β are under separate control in the prostate. A high level of CDKN2 expression was related to abnormal RB1 in one primary tumor and in the DU145 cell line, which expressed the mutated CDKN2 allele. Analysis of genomic DNA indicated that altered CDKN2 expression in primary carcinomas of the prostate was more frequently due to down-regulation of transcription (five of seven) than deletion of the gene (two of seven). Additionally, CDKN2 mRNA was induced in nonexpressor cell lines by treatment with 5-aza-2'-deoxycytidine. This study demonstrates that alteration of CDKN2 is one of the most frequent genetic abnormalities in prostate cancer and may contribute to prostate carcinogenesis.

UR - http://www.scopus.com/inward/record.url?scp=0030792699&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030792699&partnerID=8YFLogxK

M3 - Article

VL - 3

SP - 1889

EP - 1897

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 10

ER -