Human FK506 binding protein 65 is associated with colorectal cancer.
We initiated the present study to identify new genes associated with colorectal cancer. In a previously published microarray study an EST (W80763), later identified as the gene hFKBP10 (NM_021939), was found to be strongly expressed in tumors while absent in the normal mucosa. Here we describe this gene hFKBP10 together with its encoded protein hFKBP65 as a novel marker associated with colorectal cancer. Analysis of 31 colorectal adenocarcinomas and 14 normal colorectal mucosa by RealTime PCR for hFKBP10 showed a significant up-regulation in tumors, when compared with normal mucosa. Immunohistochemical analysis of 26 adenocarcinomas and matching normal mucosa, as well as benign hyperplastic polyps and adenomas, using a monoclonal anti-hFKBP65 antibody, showed that the protein was not present in normal colorectal epithelial cells, but strongly expressed in the tumor cells of colorectal cancer. The protein was also expressed in fibroblasts of both normal mucosa and tumor tissue. Western blot analysis of matched tumors and normal mucosa supported the finding of increased hFKBP65 expression in tumors compared with normal mucosa, in addition to identifying the molecular mass of hFKBP65 to approximately 72 kDa. Cellular localization and glycosylation studies revealed the hFKBP65 protein to be localized in the endoplasmic reticulum, and to be N-glycosylated. In conclusion, the protein hFKBP65 is associated with colorectal cancer, and we hypothesize the protein to be involved in fibroblast and transformed epithelial cell-specific protein synthesis in the endoplasmic reticulum.
Olesen
Sanne Harder
SH
Molecular Diagnostic Laboratory, Dept. of Clinical Biochemistry, Aarhus University Hospital, Skejby Sygehus, DK-8200 Aarhus N, Denmark.
Christensen
Lise Lotte
LL
Sørensen
Flemming Brandt
FB
Cabezón
Teresa
T
Laurberg
Søren
S
Orntoft
Torben Falck
TF
Birkenkamp-Demtröder
Karin
K
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001665:Binding Sites; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D003111:Colonic Polyps / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000166:cytology; D007526:Isoelectric Point; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D022021:Tacrolimus Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
D000911:Antibodies, Monoclonal; D022021:Tacrolimus Binding Proteins