title: Evidence for a putative senescence gene locus within the chromosomal region 10p14-p15.
abstract: High-risk human papillomavirus (HPV) types 16 and 18 are involved in the multistep process of cervical cancer. Transfection of normal keratinocytes with high-risk HPV-DNA generally gives rise to immortal cultures. This may be explained by the loss of senescence genes as a consequence of HPV-induced genetic instability. On the basis of the dominance of cellular senescence over immortality, fusion of normal keratinocytes with HPV-immortalized cells results in complementation of these putative gene defects. In a previous study, we showed that underrepresentation of chromosome 10 is a characteristic phenomenon during the early phase of immortalization. Here we show that introduction of a normal copy of chromosome 10 into HPV16-immortalized cells (HPKII) by Microcell-mediated chromosome transfer resulted in senescence of a significant number of hybrids. By using several derivatives of chromosome 10 for further fusion experiments, the chromosomal region responsible for senescence could be assigned to 10p14-p15. The potential significance of loss of gene function in this region is underlined by the high frequency (38.7%) of loss of heterozygosity in cervical cancers including early stage tumors.
authors.affiliation: Gynäkologische Molekularbiologie, Abteilung Frauenheilkunde, Frauenklinik der Friedrich-Schiller-Universität Jena, 07743 Jena, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Poignée
authors.forename: C
authors.initials: C
authors.lastname: Backsch
authors.forename: K
authors.initials: K
authors.lastname: Beer
authors.forename: L
authors.initials: L
authors.lastname: Jansen
authors.forename: N
authors.initials: N
authors.lastname: Wagenbach
authors.forename: E J
authors.initials: EJ
authors.lastname: Stanbridge
authors.forename: R
authors.initials: R
authors.lastname: Kirchmayr
authors.forename: A
authors.initials: A
authors.lastname: Schneider
authors.forename: M
authors.initials: M
authors.lastname: Dürst
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000821:virology; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D016922:Cellular Senescence / Q000235:genetics*; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D018014:Gene Transfer Techniques; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology / Q000821:virology; D019656:Loss of Heterozygosity; D027383:Papillomaviridae / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology / Q000821:virology
chemical_list: D004279:DNA, Viral