PubMed · 8051972
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A Triviño López, A López Muñiz. 1994-06-11. [Oncoprotein p53].. https://pubmed.ncbi.nlm.nih.gov/8051972/
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Recent discoveries indicate that transcriptional elongation is an important regulatory step in gene expression, and that deregulation of elongation can lead to the development of certain malignancies.
An important group of genes for the development of neoplastic diseases are, in addition to tumour suppressor genes, protooncogenes. The latter are highly preserved genes present in a similar sequence in the cell genomes of different species (yeasts - man). They encode components of biochemical signalling pathways by which external mitotic signals stimulate cell proliferation and products which inhibit cell differentiation. The result of activation of protooncogenes into oncogenes (mutations, chromosomal rearrangements, amplifications, viral insertions, insertion mutagenesis) is in particular hyperstimulation of cells resulting in uncontrolled proliferation. Mutations are of the dominant type, elimination of one allele leads to the transformation of a protooncogene into an oncogene. Oncogenes are classified with regard to the transmission level of the mitogenic signal on which they act. Originally they were detected in the genome of oncogenic viruses. However, they do not form their constant and specific constituent, the virus acts as a vector which transmits cellular protooncogenes (or oncogenes) during the reproductive cycle from one cell to another. The activity of various types of oncogenes is the necessary prerequisite for the genesis and development of various neoplastic diseases. Detection of oncogene alterations provides in some instances important diagnostic, prognostic and therapeutic findings.
Human insulin-like growth factor (IGF)-II mRNA has been shown to be expressed at high levels in a variety of tumors, including rhabdomyosarcomas. In addition, many tumors have alterations in p53 expression. To investigate whether p53 regulates IGF-II gene expression, we transfected wild-type p53 expression vectors and luciferase constructs driven by IGF-II P3 promotors into multiple cell lines. We found that p53 reduced, in a dose-dependent manner, both endogenous IGF-II P3 transcripts and transfected P3 luciferase expression. The inhibition of P3 luciferase expression by p53 was more pronounced in the two cell lines that expressed mutant p53 protein, RD, and HTB114. The element responsible for this inhibition was mapped to the minimal promoter region. We also transfected an HPV-16 E6 expression plasmid into CCL13 cells containing functional p53 and found that E6 up-regulated IGF-II P3 activity. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein to the TATA motif of P3, although both could directly associate with human TATA-binding protein. Our results suggest that p53 may play a role in regulation of IGF-II gene expression.