# CARCINOEMBRYONIC ANTIGEN--STRUCTURE-FUNCTION-REGULATION

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 1992 · $177,195

## Abstract

Carcinoembryonic antigen (CEA) is a highly-glycosylated, colonic epithelial
cell surface glycoprotein which is routinely used as a tumor marker for
colon cancer.  The sequence and domain structure of CEA, NCA (nonspecific
crossreacting antigen), and BGP (biliary glycoprotein) have been determined
by us using protein and molecular cloning studies.  All three are highly
homologous members of the immunoglobulin gene superfamily and have
suggested roles in cell-cell and bacterial-cell adhesion.  We have shown
that they are induced by gamma-interferon and tumor necrosis factor-alpha,
further suggesting a role in immunity.  As a first step in establishing the
role of these proteins, especially CEA and BGP, we will study their gene
regulation, including their induction by IFN-gamma and TNFalpha in colonic
and noncolonic cell lines.  Analyses include DNA mobility shift,
footprinting, and methylation interference assays.  We will isolate and
characterize the transcription factors responsible for the regulation of
CEA and BGP expression, and study the mechanism of IFN-gamma and TNFalpha
induction relative to other interferon responsive genes.  In continuing
structural studies, we will determine the oligosaccharide structures at
each glycosylation site and the structure of the glycosyl-
phosphatidylinositol membrane anchor and relate these structures to their
role in bacterial adhesion.  We will develop novel, rapid, sensitive
methods for the structural analysis of the transcriptional factors and
site-specific oligosaccharide units of CEA using laser desorption time of
flight mass spectrometry, and fast atom bombardment and electrospray tandem
mass spectrometry.  These methods will have general utility in the
ultrasensitive analysis of rare biological samples.  We will characterize
the Ig-like structure of CEA using expressed, secreted forms of CEA and its
individual Ig-variable and Ig-constant domains using circular dichroism and
fluorescence spectroscopy.  The structure-function relationships between
the ecto- and cytoplasmic domains of CEA, BGP, and E-Cadherin and their
role in the vectorial transport of these proteins in cell lines possessing
or defective in these properties will be determined using chimeric
constructs.  Functional assays will also include bacterial binding and
treatment with growth factors and growth factor inhibitors.  These studies
are part of a comprehension approach to the structure-function-regulation
of CEA and BGP.

## Key facts

- **NIH application ID:** 3175663
- **Project number:** 2R01CA037808-09A2
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **SAM.gov UEI:** NPH1VN32EWN5
- **Principal Investigator:** John Ernest Shively
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $177,195
- **Award type:** 2
- **Project period:** 1981-08-01 → 1995-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175663

## Citation

> US National Institutes of Health, RePORTER application 3175663, CARCINOEMBRYONIC ANTIGEN--STRUCTURE-FUNCTION-REGULATION (2R01CA037808-09A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175663. Licensed CC0.

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