title: Binding of wild-type and mutant forms of p53 protein from human tumors to a specific DNA-sequence of the first intron of the h-ras oncogene.
abstract: p53 is the most frequent target for genetic alterations in a wide variety of human cancers. The product of the p53 tumor suppressor gene binds to DNA and activates transcription from promoters containing its consensus binding site. In the accompanying paper we have found that P53 tumor suppressor protein recognizes specifically a transcriptional element within the human H-ras protooncogene (Spandidos DA, et al, Int J Oncol 7: 1029-1034, 1995). We transfected Saos-2 cells, which are p53-null cells, with plasmids encoding for the wild type (wt) and for one 'hot spot' mutant (mt) of the p53 gene (H 273). Using the resulted nuclear extracts for gel retardation assays, we showed binding of both the wild-type and the mutant form of p53 to the H-ras DNA. Furthermore, using nuclear extracts from head and neck tumors and from adjacent normal tissues in gel retardation assays, we found binding of both the wild-type and the p53 mutant in the same responsive element of the H-ras oncogene. These experimental results suggest a direct role of p53 in regulation of H-ras. Identification of cellular proto-oncogenes as mediators of the transcriptional effects of wild-type and mutant forms of p53 gene, will be a step towards a better understanding of the role of oncogenes and once-suppressor genes in tumor promotion.
authors.affiliation: NATL HELLEN RES FND,INST BIOL RES & BIOTECHNOL,GR-11635 ATHENS,GREECE. UNIV CRETE,SCH MED,IRAKLION,GREECE. DREXEL UNIV,DEPT MOLEC ONCOL,PHILADELPHIA,PA 19104.
authors.forename: V
authors.initials: V
authors.lastname: Zoumpourlis
authors.forename: G
authors.initials: G
authors.lastname: Zachos
authors.forename: T
authors.initials: T
authors.lastname: Halazonetis
authors.forename: M
authors.initials: M
authors.lastname: Ergazaki
authors.forename: D
authors.initials: D
authors.lastname: Spandidos