25 Citations (Scopus)

Abstract

The opioid growth factor (OGF), [Met5]-enkephalin, and OGF receptor (OGFr) form an inhibitory axis regulating the growth of human pancreatic cancer. This study examined whether overexpression of OGFr decreases the growth of pancreatic cells in vitro. MIA PaCa-2 cells were transfected with OGFr cDNA, and six clonal lines were examined for protein expression and function. OGFr binding assays revealed a 2.3- to 5.6-fold increase in binding capacity from wild-type (WT) and empty vector (EV) controls; binding affinity was comparable in all groups. OGFr protein expression, as measured by immunohistochemistry and Western blotting, was enhanced in clonal cell lines compared to controls. Doubling times of OGFr clonal lines were 47-91% longer than in the WT/EV groups for all but one clonal line. DNA synthesis of cells overexpressing OGFr was diminished from the WT/EV groups by 28-52%. Addition of exogenous OGF further reduced (14-31%) the cell growth of clonal lines, and the effects of exogenous OGF were receptor-mediated. Exposure of cells overexpressing OGFr to naltrexone increased the cell number by up to 9.4-fold. OGF was identified as the only opioid peptide to depress cell replication in the transfected cell lines. Neutralization of endogenous OGF with antibodies to this peptide elevated the cell number in clonal cell lines. These data identify OGFr at the molecular level as integral to regulating the cell replication of human pancreatic cancer, and support treatment modalities that amplify OGFr in order to decrease the growth of these neoplasias.

Original languageEnglish (US)
Pages (from-to)775-783
Number of pages9
JournalInternational journal of oncology
Volume30
Issue number4
StatePublished - Apr 1 2007

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Pancreatic Neoplasms
Growth
Opioid Analgesics
Intercellular Signaling Peptides and Proteins
Cell Line
methionine-enkephalin receptor
Cell Count
Naltrexone
Opioid Peptides
Enkephalins
Proteins
Complementary DNA
Western Blotting
Immunohistochemistry
Peptides
Antibodies
DNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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title = "Overexpression of the opioid growth factor receptor potentiates growth inhibition in human pancreatic cancer cells",
abstract = "The opioid growth factor (OGF), [Met5]-enkephalin, and OGF receptor (OGFr) form an inhibitory axis regulating the growth of human pancreatic cancer. This study examined whether overexpression of OGFr decreases the growth of pancreatic cells in vitro. MIA PaCa-2 cells were transfected with OGFr cDNA, and six clonal lines were examined for protein expression and function. OGFr binding assays revealed a 2.3- to 5.6-fold increase in binding capacity from wild-type (WT) and empty vector (EV) controls; binding affinity was comparable in all groups. OGFr protein expression, as measured by immunohistochemistry and Western blotting, was enhanced in clonal cell lines compared to controls. Doubling times of OGFr clonal lines were 47-91{\%} longer than in the WT/EV groups for all but one clonal line. DNA synthesis of cells overexpressing OGFr was diminished from the WT/EV groups by 28-52{\%}. Addition of exogenous OGF further reduced (14-31{\%}) the cell growth of clonal lines, and the effects of exogenous OGF were receptor-mediated. Exposure of cells overexpressing OGFr to naltrexone increased the cell number by up to 9.4-fold. OGF was identified as the only opioid peptide to depress cell replication in the transfected cell lines. Neutralization of endogenous OGF with antibodies to this peptide elevated the cell number in clonal cell lines. These data identify OGFr at the molecular level as integral to regulating the cell replication of human pancreatic cancer, and support treatment modalities that amplify OGFr in order to decrease the growth of these neoplasias.",
author = "Ian Zagon and Michael Verderame and Jody Hankins and Patricia McLaughlin",
year = "2007",
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TY - JOUR

T1 - Overexpression of the opioid growth factor receptor potentiates growth inhibition in human pancreatic cancer cells

AU - Zagon, Ian

AU - Verderame, Michael

AU - Hankins, Jody

AU - McLaughlin, Patricia

PY - 2007/4/1

Y1 - 2007/4/1

N2 - The opioid growth factor (OGF), [Met5]-enkephalin, and OGF receptor (OGFr) form an inhibitory axis regulating the growth of human pancreatic cancer. This study examined whether overexpression of OGFr decreases the growth of pancreatic cells in vitro. MIA PaCa-2 cells were transfected with OGFr cDNA, and six clonal lines were examined for protein expression and function. OGFr binding assays revealed a 2.3- to 5.6-fold increase in binding capacity from wild-type (WT) and empty vector (EV) controls; binding affinity was comparable in all groups. OGFr protein expression, as measured by immunohistochemistry and Western blotting, was enhanced in clonal cell lines compared to controls. Doubling times of OGFr clonal lines were 47-91% longer than in the WT/EV groups for all but one clonal line. DNA synthesis of cells overexpressing OGFr was diminished from the WT/EV groups by 28-52%. Addition of exogenous OGF further reduced (14-31%) the cell growth of clonal lines, and the effects of exogenous OGF were receptor-mediated. Exposure of cells overexpressing OGFr to naltrexone increased the cell number by up to 9.4-fold. OGF was identified as the only opioid peptide to depress cell replication in the transfected cell lines. Neutralization of endogenous OGF with antibodies to this peptide elevated the cell number in clonal cell lines. These data identify OGFr at the molecular level as integral to regulating the cell replication of human pancreatic cancer, and support treatment modalities that amplify OGFr in order to decrease the growth of these neoplasias.

AB - The opioid growth factor (OGF), [Met5]-enkephalin, and OGF receptor (OGFr) form an inhibitory axis regulating the growth of human pancreatic cancer. This study examined whether overexpression of OGFr decreases the growth of pancreatic cells in vitro. MIA PaCa-2 cells were transfected with OGFr cDNA, and six clonal lines were examined for protein expression and function. OGFr binding assays revealed a 2.3- to 5.6-fold increase in binding capacity from wild-type (WT) and empty vector (EV) controls; binding affinity was comparable in all groups. OGFr protein expression, as measured by immunohistochemistry and Western blotting, was enhanced in clonal cell lines compared to controls. Doubling times of OGFr clonal lines were 47-91% longer than in the WT/EV groups for all but one clonal line. DNA synthesis of cells overexpressing OGFr was diminished from the WT/EV groups by 28-52%. Addition of exogenous OGF further reduced (14-31%) the cell growth of clonal lines, and the effects of exogenous OGF were receptor-mediated. Exposure of cells overexpressing OGFr to naltrexone increased the cell number by up to 9.4-fold. OGF was identified as the only opioid peptide to depress cell replication in the transfected cell lines. Neutralization of endogenous OGF with antibodies to this peptide elevated the cell number in clonal cell lines. These data identify OGFr at the molecular level as integral to regulating the cell replication of human pancreatic cancer, and support treatment modalities that amplify OGFr in order to decrease the growth of these neoplasias.

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