Identification of two Fas-associated phosphatase-1 (FAP-1) promoters in human cancer cells.
Fas-associated phosphatase-1 (FAP-1) has been reported as a negative regulator of Fas-mediated signal transduction in human cancer cells. To obtain insights into the potential carcinogenesis of the FAP-1 gene, we investigated its transcriptional regulation in normal and cancerous cells. To identify the FAP-1 promoter sequences, we first isolated P1 and cosmid clones that contained the regulatory region upstream from the FAP-1 gene by using the PCR products of 5' rapid amplification of cDNA end (5'-RACE) as probes. Genomic analysis of positive clones revealed that the major FAP-1 mRNA was transcribed from its proximal promoter (pPRM) in all human cancer cell lines tested, but 1 additional large transcript derived from its distal promoter (dPRM) was found in the human colon cancer cell line DLD-1. This suggests that the FAP-1 gene may be aberrantly dysregulated in some types of human cancers, including colon carcinoma. Sequence analysis of the region upstream from the FAP-1 gene strongly suggests that the transcript of the FAP-1 gene may be controlled by a variety of transcriptional regulatory elements, including NF-kappa B, NF-IL6, and p53 in its 2 promoters. These results imply that the FAP-1 gene may be a target gene under the control of important apoptosis-related nuclear factors in human cancers.
Irie
S
S
Departments of Otolaryngology/Head & Neck Surgery and Pathology, Columbia University, 630 West 168th St., P&S 11-451, New York, NY 10032, USA.
Li
Y
Y
Kanki
H
H
Ohyama
T
T
Deaven
L L
LL
Somlo
S
S
Sato
T A
TA
D020121:5' Untranslated Regions; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D018076:DNA, Complementary; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D054645:Protein Phosphatase 1; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D020121:5' Untranslated Regions; D022782:CCAAT-Enhancer-Binding Protein-beta; D002352:Carrier Proteins; D018076:DNA, Complementary; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D007371:Interferon-gamma; D054645:Protein Phosphatase 1; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases