APM-1, A NOVEL HUMAN GENE, IDENTIFIED BY ABERRANT CO-TRANSCRIPTION WITH PAPILLOMAVIRUS ONCOGENES IN A CERVICAL-CARCINOMA CELL-LINE, ENCODESA BTB POZ-ZINC FINGER PROTEIN WITH GROWTH-INHIBITORY ACTIVITY/

Integration of human papillomavirus (HPV) DNA into the host cell genom e is an important step in cervical carcinogenesis, In tumour cells,vit h integrated HPV DNA, transcription of viral oncogenes Ed and E7 conti nues into the flanking cellular sequences thereby producing viral-cell ular fusion transcripts, Analysis of cellular sequences flanking the i ntegrated HPV68 DNA in the cervical carcinoma cell line ME180 revealed homozygosity of the mutant allele in ME180 cells. We speculated that this could indicate the existence of a cellular tumour suppressor gene in the integration region, We report here the identification of a nov el human gene, named APM-1, which is co-transcribed with the HPV68 Ed and E7 genes and is present in the 3'-cellular part of the ME180 viral -cellular fusion transcripts, The APM-I gene encodes a protein with a BTB/POZ domain and four zinc fingers, and is located at chromosome 18q 21, APM-I transcripts are detected in normal cervical keratinocytes, b ut not in the majority of cervical carcinoma cell lines analysed, The APM-1 gene caused a reduction of clonal cell growth in vitro of HeLa a nd CaSki tumour cells, These characteristics make APM-1, the first nov el human gene identified in a HPV integration region, a likely ate for the postulated tumour suppressor gene.