Nidogen 1 and 2 gene promoters are aberrantly methylated in human gastrointestinal cancer.

Abstract

BACKGROUND:

Nidogens are highly conserved proteins of basement membranes. Two nidogen proteins, nidogen 1 and nidogen 2, are known in mammals.

RESULTS:

We show that CpG islands of both NID1 and NID2 genes are aberrantly methylated in human cancer samples and cancer cell lines. For both genes, methylation was correlated with loss of gene transcription in human cell lines. Furthermore, demethylation of the NID1 and NID2 promoters restored gene transcription, demonstrating that methylation was responsible for silencing nidogen genes. In primary tumors, we detected NID1 promoter methylation in 67% of colon cancer samples and in 90% of gastric cancers. NID2 promoter was methylated in 29% of colon and 95% of gastric cancers. Immuno-staining for nidogen-2 confirmed the correlation between aberrant methylation and loss of nidogen expression also in primary tumors, implying that aberrant methylation was a mechanism for inhibiting nidogens expression in human gastrointestinal tumors.

CONCLUSION:

These results suggest that loss of nidogens expression has a potential pathogenetic role in colon and stomach tumorigenesis. Nidogens are believed to connect laminin and collagen IV networks, hence stabilizing the basement membrane structure. Nidogens are also important for cell adhesion, as they establish contacts with various cellular integrins. Loss of nidogen expression may favor invasion and metastasis of cancer cells by loosening cell interaction with basal membrane and by weakening the strength of the basement membrane itself, first barrier from the connective vascularized matrix.

• Authors: Linda Ulazzi, Silvia Sabbioni, Elena Miotto, Angelo Veronese, Angela Angusti, Roberta Gafà, Stefano Manfredini, Fabio Farinati, Takako Sasaki, Giovanni Lanza, Massimo Negrini
• Journal: Molecular cancer (Mol Cancer) Vol. 6 Pg. 17 (Feb 28 2007) ISSN: 1476-4598 [Electronic] England
• PMID: 17328794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• Cell Adhesion Molecules
• DNA, Neoplasm
• Membrane Glycoproteins
• NID2 protein, human
• nidogen

Topics

• Calcium-Binding Proteins
• Cell Adhesion Molecules (genetics, metabolism)
• Cell Line, Tumor
• CpG Islands (genetics)
• DNA Methylation
• DNA, Neoplasm (genetics)
• Gastrointestinal Neoplasms (genetics)
• Gene Expression Regulation, Neoplastic
• HeLa Cells
• Humans
• Immunohistochemistry
• K562 Cells
• Membrane Glycoproteins (genetics, metabolism)
• Promoter Regions, Genetic (genetics)