Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP

Wa'el El-Rifai, Michael F. Smith, Guolian Li, Andy Beckler, Virginia S. Carl, Elizabeth Montgomery, Sakari Knuutila, Christopher A. Moskaluk, Henry F. Frierson, Steven M. Powell

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Gastric carcinoma is the second most common cause of cancer-related death worldwide. Recently, we have demonstrated that expressed sequence tag AA552509 was frequently amplified and the most consistently overexpressed target at 17q in gastric cancers. Herein, we report that DARPP-32 (dopamine and cAMP-regulated phosphoprotein of Mr 32, 000) is the target gene for overexpression of expressed sequence tag AA552509. In addition, we have identified full-length cDNA of DARPP-32 (GenBank accession number AF464196) with 467 bp of additional untranslated mRNA nucleotides upstream of the previously known translation start site in exon 1. Additionally, we have discovered a novel truncated isoform of DARPP-32 that we named t-DARPP (GenBank accession number AY070271), which is also overexpressed in gastric cancers. Using quantitative real-time reverse transcription-PCR, Western blots, and staining of tumor tissue arrays, the two DARPP mRNA transcripts and proteins were overexpressed in gastric cancer cells and exhibited abundant protein overexpression in neoplastic but not normal gastric epithelial cells. DARPP-32 is the only known protein that acts as a protein phosphatase 1 inhibitor or a protein kinase A inhibitor. The novel truncated isoform, t-DARPP, lacks the phosphorylation site related to protein phosphatase 1 inhibition but maintains the phosphorylation site with the protein kinase A inhibitory effect. Our results reveal for the first time the presence of these signaling molecules in human cancer and suggest that they may be important for gastric tumorigenesis.

Original languageEnglish (US)
Pages (from-to)4061-4064
Number of pages4
JournalCancer Research
Volume62
Issue number14
StatePublished - Jul 15 2002
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    El-Rifai, W., Smith, M. F., Li, G., Beckler, A., Carl, V. S., Montgomery, E., Knuutila, S., Moskaluk, C. A., Frierson, H. F., & Powell, S. M. (2002). Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP. Cancer Research, 62(14), 4061-4064.