Overexpression of the 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein in common adenocarcinomas

Andy Beckler, Christopher A. Moskaluk, Alexander Zaika, Garret M. Hampton, Steven M. Powell, Henry F. Frierson, Wael El-Rifai

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

BACKGROUND. The 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein (DARPP-32) is the only known protein that can act as a protein phosphatase-1 inhibitor or a protein kinase inhibitor. It is known as a neurogenic protein that plays a major role in dopamine regulation in the central nervous system. Recently, DARPP-32 and a truncated isoform, t-DARPP, have been cloned in gastric carcinoma. The extent of DARPP-32 and t-DARPP expression in human epithelial tissues and carcinomas remained unknown. METHODS. Using tissue microarrays and an antibody to DARPP-32, the authors evaluated the immunohistochemical findings in 43 different normal epithelium human tissue samples and in 187 samples of common carcinomas of breast, prostate, colon, and stomach. RESULTS. DARPP-32 proteins were expressed at varying levels in several types of normal epithelial tissues outside of the central nervous system. Using quantitative real-time reverse transcriptase-polymerase chain reaction analysis, the authors demonstrated that both DARPP-32 and t-DARPP mRNAs frequently were overexpressed in carcinomas of the breast, prostate, colon, and stomach compared with normal tissue samples. Immunohistochemical analysis of tissue microarrays that contained 187 carcinoma samples confirmed the strong expression of DARPP-32 proteins in these tumor types. CONCLUSIONS. The current study provides the first evidence that DARPP-32 expression is not limited to dopamine signaling in normal cells of the central nervous system. The pattern of expression of DARPP-32 proteins in normal epithelial tissues suggests that these proteins play an important role in epithelial signaling that may be tissue specific. Moreover, the observation that DARPP-32 and t-DARPP frequently are overexpressed in common subtypes of human adenocarcinomas suggest that these proteins may be important in tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1547-1551
Number of pages5
JournalCancer
Volume98
Issue number7
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

Fingerprint

Dopamine and cAMP-Regulated Phosphoprotein 32
Phosphoproteins
Adenosine
Dopamine
Adenocarcinoma
Epithelium
Stomach
Central Nervous System
Carcinoma
Prostate
Colon
Proteins
Tissue Array Analysis
Breast Neoplasms
Protein Kinase Inhibitors
Reverse Transcriptase Polymerase Chain Reaction
Real-Time Polymerase Chain Reaction
Protein Isoforms
Carcinogenesis
Messenger RNA

Keywords

  • 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein
  • Adenocarcinoma
  • Immunohistochemistry
  • Reverse transcriptase-polymerase chain reaction

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Overexpression of the 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein in common adenocarcinomas. / Beckler, Andy; Moskaluk, Christopher A.; Zaika, Alexander; Hampton, Garret M.; Powell, Steven M.; Frierson, Henry F.; El-Rifai, Wael.

In: Cancer, Vol. 98, No. 7, 01.10.2003, p. 1547-1551.

Research output: Contribution to journalArticle

Beckler, Andy ; Moskaluk, Christopher A. ; Zaika, Alexander ; Hampton, Garret M. ; Powell, Steven M. ; Frierson, Henry F. ; El-Rifai, Wael. / Overexpression of the 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein in common adenocarcinomas. In: Cancer. 2003 ; Vol. 98, No. 7. pp. 1547-1551.
@article{4ab6e57d3bfa43d79f74b5b95cc560aa,
title = "Overexpression of the 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein in common adenocarcinomas",
abstract = "BACKGROUND. The 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein (DARPP-32) is the only known protein that can act as a protein phosphatase-1 inhibitor or a protein kinase inhibitor. It is known as a neurogenic protein that plays a major role in dopamine regulation in the central nervous system. Recently, DARPP-32 and a truncated isoform, t-DARPP, have been cloned in gastric carcinoma. The extent of DARPP-32 and t-DARPP expression in human epithelial tissues and carcinomas remained unknown. METHODS. Using tissue microarrays and an antibody to DARPP-32, the authors evaluated the immunohistochemical findings in 43 different normal epithelium human tissue samples and in 187 samples of common carcinomas of breast, prostate, colon, and stomach. RESULTS. DARPP-32 proteins were expressed at varying levels in several types of normal epithelial tissues outside of the central nervous system. Using quantitative real-time reverse transcriptase-polymerase chain reaction analysis, the authors demonstrated that both DARPP-32 and t-DARPP mRNAs frequently were overexpressed in carcinomas of the breast, prostate, colon, and stomach compared with normal tissue samples. Immunohistochemical analysis of tissue microarrays that contained 187 carcinoma samples confirmed the strong expression of DARPP-32 proteins in these tumor types. CONCLUSIONS. The current study provides the first evidence that DARPP-32 expression is not limited to dopamine signaling in normal cells of the central nervous system. The pattern of expression of DARPP-32 proteins in normal epithelial tissues suggests that these proteins play an important role in epithelial signaling that may be tissue specific. Moreover, the observation that DARPP-32 and t-DARPP frequently are overexpressed in common subtypes of human adenocarcinomas suggest that these proteins may be important in tumorigenesis.",
keywords = "32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein, Adenocarcinoma, Immunohistochemistry, Reverse transcriptase-polymerase chain reaction",
author = "Andy Beckler and Moskaluk, {Christopher A.} and Alexander Zaika and Hampton, {Garret M.} and Powell, {Steven M.} and Frierson, {Henry F.} and Wael El-Rifai",
year = "2003",
month = "10",
day = "1",
doi = "10.1002/cncr.11654",
language = "English (US)",
volume = "98",
pages = "1547--1551",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

TY - JOUR

T1 - Overexpression of the 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein in common adenocarcinomas

AU - Beckler, Andy

AU - Moskaluk, Christopher A.

AU - Zaika, Alexander

AU - Hampton, Garret M.

AU - Powell, Steven M.

AU - Frierson, Henry F.

AU - El-Rifai, Wael

PY - 2003/10/1

Y1 - 2003/10/1

N2 - BACKGROUND. The 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein (DARPP-32) is the only known protein that can act as a protein phosphatase-1 inhibitor or a protein kinase inhibitor. It is known as a neurogenic protein that plays a major role in dopamine regulation in the central nervous system. Recently, DARPP-32 and a truncated isoform, t-DARPP, have been cloned in gastric carcinoma. The extent of DARPP-32 and t-DARPP expression in human epithelial tissues and carcinomas remained unknown. METHODS. Using tissue microarrays and an antibody to DARPP-32, the authors evaluated the immunohistochemical findings in 43 different normal epithelium human tissue samples and in 187 samples of common carcinomas of breast, prostate, colon, and stomach. RESULTS. DARPP-32 proteins were expressed at varying levels in several types of normal epithelial tissues outside of the central nervous system. Using quantitative real-time reverse transcriptase-polymerase chain reaction analysis, the authors demonstrated that both DARPP-32 and t-DARPP mRNAs frequently were overexpressed in carcinomas of the breast, prostate, colon, and stomach compared with normal tissue samples. Immunohistochemical analysis of tissue microarrays that contained 187 carcinoma samples confirmed the strong expression of DARPP-32 proteins in these tumor types. CONCLUSIONS. The current study provides the first evidence that DARPP-32 expression is not limited to dopamine signaling in normal cells of the central nervous system. The pattern of expression of DARPP-32 proteins in normal epithelial tissues suggests that these proteins play an important role in epithelial signaling that may be tissue specific. Moreover, the observation that DARPP-32 and t-DARPP frequently are overexpressed in common subtypes of human adenocarcinomas suggest that these proteins may be important in tumorigenesis.

AB - BACKGROUND. The 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein (DARPP-32) is the only known protein that can act as a protein phosphatase-1 inhibitor or a protein kinase inhibitor. It is known as a neurogenic protein that plays a major role in dopamine regulation in the central nervous system. Recently, DARPP-32 and a truncated isoform, t-DARPP, have been cloned in gastric carcinoma. The extent of DARPP-32 and t-DARPP expression in human epithelial tissues and carcinomas remained unknown. METHODS. Using tissue microarrays and an antibody to DARPP-32, the authors evaluated the immunohistochemical findings in 43 different normal epithelium human tissue samples and in 187 samples of common carcinomas of breast, prostate, colon, and stomach. RESULTS. DARPP-32 proteins were expressed at varying levels in several types of normal epithelial tissues outside of the central nervous system. Using quantitative real-time reverse transcriptase-polymerase chain reaction analysis, the authors demonstrated that both DARPP-32 and t-DARPP mRNAs frequently were overexpressed in carcinomas of the breast, prostate, colon, and stomach compared with normal tissue samples. Immunohistochemical analysis of tissue microarrays that contained 187 carcinoma samples confirmed the strong expression of DARPP-32 proteins in these tumor types. CONCLUSIONS. The current study provides the first evidence that DARPP-32 expression is not limited to dopamine signaling in normal cells of the central nervous system. The pattern of expression of DARPP-32 proteins in normal epithelial tissues suggests that these proteins play an important role in epithelial signaling that may be tissue specific. Moreover, the observation that DARPP-32 and t-DARPP frequently are overexpressed in common subtypes of human adenocarcinomas suggest that these proteins may be important in tumorigenesis.

KW - 32-kilodalton dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein

KW - Adenocarcinoma

KW - Immunohistochemistry

KW - Reverse transcriptase-polymerase chain reaction

UR - http://www.scopus.com/inward/record.url?scp=0141675066&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141675066&partnerID=8YFLogxK

U2 - 10.1002/cncr.11654

DO - 10.1002/cncr.11654

M3 - Article

VL - 98

SP - 1547

EP - 1551

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 7

ER -