An alternatively spliced form of apobec-1 messenger RNA is overexpressed in human colon cancer.
OBJECTIVE
Apobec-1 is an RNA-specific cytidine deaminase whose forced overexpression in transgenic animals is associated with hepatic carcinogenesis. Apobec-1 messenger RNA (mRNA) undergoes alternative splicing, generating a catalytically inactive peptide, apobec-T. We have examined apobec-1 gene expression in human gastrointestinal tumors and in colon cancer-derived cell lines.


METHODS
Levels of the full-length (apobec-1) and alternatively spliced (apobec-T) mRNAs were measured by RNase protection assay, and apobec-T distribution was determined by immunocytochemical localization.


RESULTS
Apobec-1 mRNA was detectable in normal and colon cancer tissue, metastatic nodules, and certain colon cancer-derived cell lines. Apobec-T mRNA abundance was increased an average of 3.5-fold in colon cancers compared with paired control tissue (range, 0.5-14-fold). Immunocytochemical analysis showed apobec-T expression in normal fetal and adult colon and in gastric and small intestinal adenocarcinomas, colonic tubular adenomas, and both primary and metastatic colonic tumors. Overexpression of apobec-T in a tetracycline-responsive cell line decreased cellular proliferation.


CONCLUSIONS
Apobec-T is expressed in normal, adenomatous, and cancerous gastrointestinal tissues, and levels of the mRNA encoding this peptide are significantly increased in colon cancer. Although its relationship to colon carcinogenesis has not been defined, the regulated overexpression of apobec-T is associated with an altered growth phenotype.
Lee
R M
RM
Department of Medicine, University of Chicago, Chicago, Illinois, USA.
Hirano
K
K
Anant
S
S
Baunoch
D
D
Davidson
N O
NO
D016475:3T3 Cells / Q000378:metabolism; D000071479:APOBEC-1 Deaminase; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics; D012016:Reference Values; D014407:Tumor Cells, Cultured; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase