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

Wael 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

74 Citations (Scopus)

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

Fingerprint

Dopamine and cAMP-Regulated Phosphoprotein 32
Stomach Neoplasms
Protein Isoforms
Stomach
Expressed Sequence Tags
Nucleic Acid Databases
Cyclic AMP-Dependent Protein Kinases
Phosphorylation
Protein Phosphatase 1
Neoplasms
Messenger RNA
Proteins
Protein Kinase Inhibitors
Reverse Transcription
Exons
Carcinogenesis
Nucleotides
Complementary DNA
Western Blotting
Epithelial Cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP. / El-Rifai, Wael; Smith, Michael F.; Li, Guolian; Beckler, Andy; Carl, Virginia S.; Montgomery, Elizabeth; Knuutila, Sakari; Moskaluk, Christopher A.; Frierson, Henry F.; Powell, Steven M.

In: Cancer Research, Vol. 62, No. 14, 15.07.2002, p. 4061-4064.

Research output: Contribution to journalArticle

El-Rifai, W, Smith, MF, Li, G, Beckler, A, Carl, VS, Montgomery, E, Knuutila, S, Moskaluk, CA, Frierson, HF & Powell, SM 2002, 'Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP', Cancer Research, vol. 62, no. 14, pp. 4061-4064.
El-Rifai W, Smith MF, Li G, Beckler A, Carl VS, Montgomery E et al. Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP. Cancer Research. 2002 Jul 15;62(14):4061-4064.
El-Rifai, Wael ; Smith, Michael F. ; Li, Guolian ; Beckler, Andy ; Carl, Virginia S. ; Montgomery, Elizabeth ; Knuutila, Sakari ; Moskaluk, Christopher A. ; Frierson, Henry F. ; Powell, Steven M. / Gastric cancers overexpress DARPP-32 and a novel isoform, t-DARPP. In: Cancer Research. 2002 ; Vol. 62, No. 14. pp. 4061-4064.
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AU - Montgomery, Elizabeth

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