Grant Details
Grant Number: |
7R29CA070335-06 Interpret this number |
Primary Investigator: |
Frucht, Harold |
Organization: |
Columbia University Health Sciences |
Project Title: |
Regulation of Gastrin Receptors on Gi Cancer Cells |
Fiscal Year: |
2000 |
Abstract
DESCRIPTION: The aim of the present research is to determine the mechanism
by which receptors of the gastrin family of peptides confer a growth
advantage on gastrointestinal malignancies. The experiments will determine
whether conferred growth is a result of normal receptor ligand binding or a
result of abnormalities of the gastrin receptor. We will determine the role
of receptor expression regulation, such as up or down regulation and
internalization, as well as the role of abnormally expressed receptors, the
role of receptors specific for ligands other than gastrin, whether there is
a functional uncoupling of receptor binding from receptor expression, or
whether a combination of these exist and accounts for the growth stimulation
of gastrointestinal tumors. The specific aims are as follows: 1) Determine
the expression and the dynamics of expression of gastrin receptors on human
colon and gastric cancer cells. We will determine the expression of gastrin
receptor transcript and protein. This will be correlated with peptide
binding studies to determine whether a functional uncoupling exists. This
will be accomplished by Northern analysis, TR-PCR, antibody
immunofluorescence, ligand binding, and Southern analysis. Cultured cells
and surgical specimens will be utilized. 2) Determine the mitogenic effect
of the gastrin receptor on human colon and gastric cancer cells. Cells
bearing receptors which maintain a normal binding and expression
relationship will be characterized by proliferation assays using specific
receptor agonists and antagonists. Cells bearing receptors which do not
exhibit a receptor binding-expression relationship will be studied in
proliferation assays using anti-sense constructs. 3) Demonstrate the
interaction of gastrointestinal peptides with gastrin and the gastrin
receptor on human colon and gastric cancer cells. Peptide and receptors
other than those of the gastrin family will be analyzed for a possible
effect on the dynamics of gastrin receptor expression. This will be
accomplished using biochemical and molecular probes for the bombesin, VIP,
and muscarinic cholinergic families of peptide and neurotransmitters.
Determinations will be performed by Northern and Southern analysis, and
radiolabelled ligand binding.
Publications
Cholinergic receptor up-regulates COX-2 expression and prostaglandin E(2) production in colon cancer cells.
Authors: Yang W.L.
, Frucht H.
.
Source: Carcinogenesis, 2000 Oct; 21(10), p. 1789-93.
PMID: 11023534
Related Citations
Human colon cancer cell proliferation mediated by the M3 muscarinic cholinergic receptor.
Authors: Frucht H.
, Jensen R.T.
, Dexter D.
, Yang W.L.
, Xiao Y.
.
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 1999 Sep; 5(9), p. 2532-9.
PMID: 10499630
Related Citations