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.
Ikeda
Koei
K
Department of Surgical Pathology, Kumamoto University School of Medicine, Japan.
Iyama
Ken-ichi
K
Ishikawa
Nobuyuki
N
Egami
Hiroshi
H
Nakao
Mitsuyoshi
M
Sado
Yoshikazu
Y
Ninomiya
Yoshifumi
Y
Baba
Hideo
H
D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000494:pharmacology; D001485:Basement Membrane / Q000378:metabolism; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D015536:Down-Regulation; D004338:Drug Combinations; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D017930:Genes, Reporter; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
C478159:COL4A5 protein, human; D024141:Collagen Type IV; D004273:DNA, Neoplasm; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D003094:Collagen; D001374:Azacitidine