TRANSCRIPTIONAL REPRESSION OF THE NEU PROTOONCOGENE BY THE ADENOVIRUS-5 E1A GENE-PRODUCTS

Amplification/overexpression of the human protooncogene has been frequently found in human primary breast and ovarian cancers and is correlated with the ber of axillary lymph nodes positive for metastasis in st cancer patients. Identification of the factors controlling transcription of the neu gene is essential for understanding the mechanisms of neu gene regulation and its role in tumorigenity. The adenovirus early region 1A (E1A) gene products are tropic transcription regulators of viral and cellular genes have been identified as a viral suppressor gene for meis. Here we demonstrate that transcription of neu can be gly repressed by the E1A gene products. The 13S and 12S ducts of E1A gene are effective at repressing neu transcription and the transcriptional repression requires the conserved en 2 of the E1A proteins. The target for E1A repression was lized within a 139-base-pair DNA fragment in the upstream an of the neu promoter. In addition, competition experiments suggest that the sequence TGGAATG, within the 139-one-pair fragment, is an important element for the E1A-duced repression. These results indicate that E1A negatively lates neu gene expression at the transcriptional level by ns of a specific DNA element.