Cyclin D1 gene contains a cryptic promoter that is functional in human cancer cells

A novel cyclin D1 (CCND1)-TROP2 fusion oncogene has been isolated from huma n cancer cells. Unexpectedly, the chimeric cDNA was found to express TROP2 in the absence of exogenous promoters. Mutagenesis of the TROP2 and CCND1 s equences and in vitro transcription/translation show that a cryptic promote r is present in the 3 ' coding region of CCND1. The CCND1 cryptic promoter is functional in luciferase assays, where it augments the basal expression levels by eightfold and efficiently cooperates with an SV-40 enhancer. The transcription start sites of the cryptic promoter map at bases 797 and 935 of CCND1, as determined by RNase protection assays. The cryptic promoter po ssesses canonical binding sites for ubiquitous transcription factors and W/ S, XI, and CAAT/Y boxes that are characteristic of major histocompatibility complex class II gene promoters. Remarkably, the cryptic CCND1 promoter is active in human cancer cells and generates a truncated transcript that con tains CCND1 instability sequences. Thus, this novel CCND1 transcription uni t may play a role in the regulation of the expression of cyclin D1 and in t umor cell growth, (C) 2001 Wiley-Liss, Inc.