The mismatch repair gene hMSH2 is mutated in the prostate cancer cell line LNCaP

Fredrick S. Leach, Alfredo Velasco, Jer-Tsong Hsieh, Arthur I Sagalowsky, John D. McConnell

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Purpose: Mismatch repair genes are responsible for the coordinated correction of misincorporated nucleotides formed during DNA replication. Inactivating and inherited mutations in the prototypic mismatch repair gene hMSH2 have been described in a cancer predisposition syndrome known as hereditary nonpolyposis colon cancer. Patients with hereditary nonpolyposis colon cancer are at increased risk for colon cancer and extracolonic cancers such as upper tract transitional cell carcinoma but not prostate cancer. We investigated expression of hMSH2 in prostate cancer cell lines using genetic and molecular analysis. Materials and Methods: We used the 3 well described prostate cancer cell lines, DU145, LNCaP and PC3. Western blot analysis with monoclonal antibody to hMSH2 was used to assess expression. Southern blot and polymerase chain reaction of genomic DNA were used to identify genetic alterations in the hMSH2 gene. Single cell cloning, dinucleotide repeats and BAT-26 were used to assess the cell lines for microsatellite instability. Results: The prostate cancer cell line LNCaP did not express hMSH2 and was found to have a homozygous deletion of hMSH2 exons 9 to 16, resulting in truncation of the protein. While microsatellite analysis did not reveal alterations at the BAT-26 locus, single cell cloning produced several LNCaP subclones with alteration at 1 dinucleotide repeat. Conclusions: The well described prostate cancer cell line LNCaP has a mutation in the hMSH2 gene, resulting in loss of expression and possible evidence of microsatellite instability. To our knowledge our finding is the first demonstration of a genetic alteration in hMSH2 in a prostate cancer cell line.

Original languageEnglish (US)
Pages (from-to)1830-1833
Number of pages4
JournalJournal of Urology
Volume164
Issue number5
StatePublished - 2000

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DNA Mismatch Repair
Prostatic Neoplasms
Cell Line
Genes
Dinucleotide Repeats
Hereditary Nonpolyposis Colorectal Neoplasms
Microsatellite Instability
Organism Cloning
Mutation
Transitional Cell Carcinoma
Southern Blotting
DNA Replication
Microsatellite Repeats
Colonic Neoplasms
Molecular Biology
Exons
Neoplasms
Nucleotides
Western Blotting
Monoclonal Antibodies

Keywords

  • Base pair mismatch
  • DNA repair
  • Microsatellite repeats
  • Prostatic neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

The mismatch repair gene hMSH2 is mutated in the prostate cancer cell line LNCaP. / Leach, Fredrick S.; Velasco, Alfredo; Hsieh, Jer-Tsong; Sagalowsky, Arthur I; McConnell, John D.

In: Journal of Urology, Vol. 164, No. 5, 2000, p. 1830-1833.

Research output: Contribution to journalArticle

Leach, Fredrick S. ; Velasco, Alfredo ; Hsieh, Jer-Tsong ; Sagalowsky, Arthur I ; McConnell, John D. / The mismatch repair gene hMSH2 is mutated in the prostate cancer cell line LNCaP. In: Journal of Urology. 2000 ; Vol. 164, No. 5. pp. 1830-1833.
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abstract = "Purpose: Mismatch repair genes are responsible for the coordinated correction of misincorporated nucleotides formed during DNA replication. Inactivating and inherited mutations in the prototypic mismatch repair gene hMSH2 have been described in a cancer predisposition syndrome known as hereditary nonpolyposis colon cancer. Patients with hereditary nonpolyposis colon cancer are at increased risk for colon cancer and extracolonic cancers such as upper tract transitional cell carcinoma but not prostate cancer. We investigated expression of hMSH2 in prostate cancer cell lines using genetic and molecular analysis. Materials and Methods: We used the 3 well described prostate cancer cell lines, DU145, LNCaP and PC3. Western blot analysis with monoclonal antibody to hMSH2 was used to assess expression. Southern blot and polymerase chain reaction of genomic DNA were used to identify genetic alterations in the hMSH2 gene. Single cell cloning, dinucleotide repeats and BAT-26 were used to assess the cell lines for microsatellite instability. Results: The prostate cancer cell line LNCaP did not express hMSH2 and was found to have a homozygous deletion of hMSH2 exons 9 to 16, resulting in truncation of the protein. While microsatellite analysis did not reveal alterations at the BAT-26 locus, single cell cloning produced several LNCaP subclones with alteration at 1 dinucleotide repeat. Conclusions: The well described prostate cancer cell line LNCaP has a mutation in the hMSH2 gene, resulting in loss of expression and possible evidence of microsatellite instability. To our knowledge our finding is the first demonstration of a genetic alteration in hMSH2 in a prostate cancer cell line.",
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