The claudin gene family

Expression in normal and neoplastic tissues

Kyle J Hewitt, Rachana Agarwal, Patrice J. Morin

Research output: Contribution to journalArticle

330 Citations (Scopus)

Abstract

Background: The claudin (CLDN) genes encode a family of proteins important in tight junction formation and function. Recently, it has become apparent that CLDN gene expression is frequently altered in several human cancers. However, the exact patterns of CLDN expression in various cancers is unknown, as only a limited number of CLDN genes have been investigated in a few tumors. Methods: We identified all the human CLDN genes from Genbank and we used the large public SAGE database to ascertain the gene expression of all 21 CLDN in 266 normal and neoplastic tissues. Using real-time RT-PCR, we also surveyed a subset of 13 CLDN genes in 24 normal and 24 neoplastic tissues. Results: We show that claudins represent a family of highly related proteins, with claudin-16, and -23 being the most different from the others. From in silico analysis and RT-PCR data, we find that most claudin genes appear decreased in cancer, while CLDN3, CLDN4, and CLDN7 are elevated in several malignancies such as those originating from the pancreas, bladder, thyroid, fallopian tubes, ovary, stomach, colon, breast, uterus, and the prostate. Interestingly, CLDN5 is highly expressed in vascular endothelial cells, providing a possible target for antiangiogenic therapy. CLDN18 might represent a biomarker for gastric cancer. Conclusion: Our study confirms previously known CLDN gene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that express CLDN3 and CLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4.

Original languageEnglish (US)
Article number186
JournalBMC Cancer
Volume6
DOIs
StatePublished - Dec 1 2006

Fingerprint

Gene Expression
Neoplasms
Genes
Claudin-3
Claudin-4
Claudins
Fallopian Tubes
Tight Junctions
Nucleic Acid Databases
Computer Simulation
Stomach Neoplasms
Uterus
Real-Time Polymerase Chain Reaction
Prostate
Pancreas
Ovary
Stomach
Thyroid Gland
Colon
Urinary Bladder

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The claudin gene family : Expression in normal and neoplastic tissues. / Hewitt, Kyle J; Agarwal, Rachana; Morin, Patrice J.

In: BMC Cancer, Vol. 6, 186, 01.12.2006.

Research output: Contribution to journalArticle

Hewitt, Kyle J ; Agarwal, Rachana ; Morin, Patrice J. / The claudin gene family : Expression in normal and neoplastic tissues. In: BMC Cancer. 2006 ; Vol. 6.
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