Truncating mutations in the ACVR2 gene attenuates activin signaling in prostate cancer cells

Michael R. Rossi, Yurij Ionov, Andrei V. Bakin, John Kenneth Cowell

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Activins are classified as members of the TGFβ superfamily of signaling molecules and both activin and TGFβ ligands signal through structurally and functionally related serine/threonine kinase receptors. Defects in these signaling pathways have been associated with the initiation and progression of the cancer phenotype. Inactivating mutations in the TGFβ type II receptor gene, TGFβR2, have been identified in a variety of tumors and cell lines, particularly those with microsatellite instability (MSI). More recently, mutations in the activin type II receptor gene, ACVR2, were identified in colon and pancreatic cell lines and tumors with MSI. Because prostate tumors appear to have a high incidence of MSI, we analyzed prostate cancer cell lines, with and without MSI, for ACVR2 and TGFβR2 mutations. Our analysis of 6 prostate cell lines revealed mutations in the ACVR2 gene in 22Rv-1, LAPC-4, DU145, and LNCaP cells and mutations in the TGFβR2 gene in 22Rv-1 and LAPC-4. PC3 and H660 cells were wild-type for ACVR2 and TFGβR2. All of the ACVR2 mutations were truncating mutations, and using an activin response assay, we demonstrate that truncating mutations of the ACVR2 gene result in a significant reduction in activin mediated cell signaling. Inactivation of ACVR2 is a common event in prostate cancer cells suggesting it may play an important role in the development of prostate cancer.

Original languageEnglish (US)
Pages (from-to)123-129
Number of pages7
JournalCancer Genetics and Cytogenetics
Volume163
Issue number2
DOIs
StatePublished - Dec 1 2005
Externally publishedYes

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Activins
Prostatic Neoplasms
Microsatellite Instability
Mutation
Genes
Tumor Cell Line
Prostate
Type II Activin Receptors
Cell Line
Protein-Serine-Threonine Kinases
Neoplasms
Colon
Ligands
Phenotype
Incidence

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Truncating mutations in the ACVR2 gene attenuates activin signaling in prostate cancer cells. / Rossi, Michael R.; Ionov, Yurij; Bakin, Andrei V.; Cowell, John Kenneth.

In: Cancer Genetics and Cytogenetics, Vol. 163, No. 2, 01.12.2005, p. 123-129.

Research output: Contribution to journalArticle

Rossi, Michael R. ; Ionov, Yurij ; Bakin, Andrei V. ; Cowell, John Kenneth. / Truncating mutations in the ACVR2 gene attenuates activin signaling in prostate cancer cells. In: Cancer Genetics and Cytogenetics. 2005 ; Vol. 163, No. 2. pp. 123-129.
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