PubMed · 3064427
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O G Andzhaparidze, E R Pille. [Human lymphoblastoid interferon].. https://pubmed.ncbi.nlm.nih.gov/3064427/
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The v-ski oncogene promotes cellular transformation and myogenic differentiation. In quail embryo fibroblasts the two properties are displayed simultaneously and terminal muscle differentiation occurs only among cells already transformed by v-ski. To understand how the two phenotypes are derived from a single gene, we have undertaken to identify functionally important regions in v-ski and to test whether these regions can promote one phenotype without the other. We have generated both random and targeted mutations in v-ski and evaluated the effects of these mutations on expression, intracellular location, transformation, and myogenesis. Among a total of 26 mutants analysed, we have not found complete separation of the myogenic and transforming properties. Mutations in the region of v-Ski encoded by exon 1 of c-ski frequently abolish both its transformation and muscle differentiation activities, whereas mutations outside of this region are always tolerated. When expressed in cells from a minigene containing only the exon 1 sequence, the protein displays the transforming and myogenic activities similar to v-Ski. These results argue that the amino acid sequence encoded by exon 1 contains the core functional domain of the oncoprotein. To determine whether this functional domain has a structural counterpart, we have fragmented the v-Ski protein by limited proteolysis and found a single proteolytically stable domain spanning the entire exon 1-encoded region. Physical studies of the polypeptide encoded by exon 1 confirms that it folds into a compact, globular protein. The finding that both the transforming and myogenic properties of v-Ski are inseparable by mutation and are contained in a single domain suggests that they are derived from the same function.
Perhaps the most promising lead to the prevention of cancer is derived from the epidemiologic observations that vegetables and fruit are consistently associated with lower risk of cancers of most epithelia. Over 200 studies have been undertaken, and a high proportion of them show lower risk with greater consumption. There are many plausible pathways to explain this risk reduction. The initial human experiments with specific single agents have proved to be disappointing. Single agents are not an advocated approach to chemotherapy, and may be inappropriate for chemoprevention. Foods may provide the optimal mix of phytochemicals and the best polypharmacy against the emergence of malignant clones.
BACKGROUND: Little is known about the genetic events in the malignant transformation of prostatic cells. This is due in large measure to the cellular heterogeneity of the prostate. METHODS: An amplification method was devised to synthesize cDNA from small samples of cancer and benign tissues of the same resected glands. Differential gene expression of candidate informative markers between cancer and benign was screened by the polymerase chain reaction with gene-specific oligonucleotide primers. RESULTS: The expression of a transcription factor, ETS-2, was shown to be elevated in some cancer specimens. Elevated expression was also noted for neuron-specific enolase (NSE) and another transcription factor, SEF2. CONCLUSIONS: Our method can be used to identify quickly genes that are differentially expressed between benign and cancerous prostate cells. Transcription factors, such as ETS-2, may play a significant role in cancer progression.