CLONING, SEQUENCE, AND DEVELOPMENTAL EXPRESSION ANALYSIS OF C4-2, A POTENTIAL BRAIN TUMOR-SUPPRESSOR GENE

Background: Previously, we reported the isolation of C4-2 as a potenti al tumor suppressor gene in human brain tumors, To understand the func tion of this gene, we investigated its molecular characterization and expression during development. Methods: Human fetal brain library scre ening and 5'RACE-PCR method was used to isolate the full-length cDNA. The coding region of C4-2 was used for in situ hybridization to study its expression during development. Results: We report here the complet e sequence of this gene. Sequence analysis indicated that C4-2 has a 9 4% sequence identity to a family of cAMP-regulated phosphoproteins (AR PP-16/19) in the coding region. C4-2 has a 3.1 Kb long 3'UTR with vari able identity to ARPP-16 and ARPP-19. Northern blot analysis indicated that C4-2 is expressed at high levels in normal brain compared to oth er tissues. Zoo blot analysis demonstrated that the coding region of C 4-2 is highly conserved among different animals. In situ hybridization using C4-2 coding region demonstrated that it follows a unique expres sion pattern during mouse brain development. High level of C4-2 expres sion was also observed in the spinal cord and somites of the developin g embryo. Conclusion: Expression analysis during brain development str ongly suggests that this family of proteins may play an important role not only in normal functioning of the brain, but also during brain de velopment. (C) 1997 Wiley-Liss, Inc.