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 regula tor of Fas-mediated signal transduction in human cancer cells. To obtain in sights into the potential carcinogenesis of the FAP-I 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 c ontained the regulatory region upstream from the FAP-1 gene by using the PC R products of 5 ' rapid amplification of cDNA end (T-RACE) as probes. Genom ic analysis of positive clones revealed that the major FAP-1 mRNA was trans cribed from its proximal promoter (pPRM) in all human cancer cell lines tes ted, but 1 additional large transcript derived from its distal promoter (dP RM) 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 cance rs, including colon carcinoma. Sequence analysis of the region upstream fro m the FAP-1 gene strongly suggests that the transcript of the FAP-1 gene ma y be controlled by a variety of transcriptional regulatory elements, includ ing NF-kappaB, 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 apoptos is-related nuclear factors in human cancers.