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Ikeda, K. et al.

Loss of expression of type IV collagen alpha5 and alpha6 chains in colorectal cancer associated with the hypermethylation of their promoter region.

Type IV collagen, a major component of the basement membrane (BM), is composed of six genetically distinct alpha(IV) chains, alpha1(IV) to alpha6(IV). Their genes are paired on three different chromosomes in a head-to-head arrangement. The alpha5(IV) gene (COL4A5) and the alpha6(IV) gene (COL4A6) are on chromosome Xq22 and are regulated by a bidirectional promoter. Loss of the alpha5(IV)/alpha6(IV) chains in epithelial BM occur in the early stage of cancer invasion. However, the regulatory mechanism of the specific loss of the alpha5(IV)/alpha6(IV) chains during cancer cell invasion is still undetermined. In the present study, we examined the expression of the alpha5(IV)/alpha6(IV) chains and the methylation profiles of the bidirectional promoter region of COL4A5/COL4A6 in colon cancer cell lines and colorectal tumor tissues. The expression of the alpha5(IV)/alpha6(IV) chains was down-regulated in colorectal cancer, and the loss of expression of the alpha5(IV)/alpha6(IV) chains was associated with the hypermethylation of their promoter region. In conclusion, the hypermethylation of the bidirectional promoter region of COL4A5/COL4A6 is one of the events that is responsible for the loss of expression of the alpha5(IV)/alpha6(IV) chains and the remodeling of the epithelial BM during cancer cell invasion.[1]

References

Loss of expression of type IV collagen alpha5 and alpha6 chains in colorectal cancer associated with the hypermethylation of their promoter region. Ikeda, K., Iyama, K., Ishikawa, N., Egami, H., Nakao, M., Sado, Y., Ninomiya, Y., Baba, H. Am. J. Pathol. (2006) [Pubmed]

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