Oncogenes in solid human tumours

Pulciani, Simonetta; Santos, Eugenio; Lauver, Anne V.; Long, Linda K.; Aaronson, Stuart A.; Barbacid, Mariano

doi:10.1038/300539a0

Cited by 449 publications

(225 citation statements)

References 26 publications

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“…See the legend to Fig. 1 (6,8,11,15,19,23 After the completion of this study, a report appeared which described active Ki-ras oncogenes in 3-MC-induced mouse fibrosarcomas. This report (8) …”

Section: MCmentioning

confidence: 99%

Presence of a Kirsten murine sarcoma virus ras oncogene in cells transformed by 3-methylcholanthrene.

Parada¹,

Weinberg²

1983

Mol. Cell. Biol.

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Section: MCmentioning

confidence: 99%

Presence of a Kirsten murine sarcoma virus ras oncogene in cells transformed by 3-methylcholanthrene.

Parada¹,

Weinberg²

1983

Mol. Cell. Biol.

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“…12 In addition to these characteristic genetic alterations, a subset of early-onset RMS is associated with germline mutations of the p53 tumor suppressor, 13 and mutations of the Ras and Met oncogenes are commonly observed in sporadic RMS. [14][15][16] Head and neck RMS is more often seen in younger children and is more likely to be embryonal, while tumors of the extremities are more common in adolescents and tend to be alveolar. 17 Both RMS types are highly malignant, but alveolar RMS is associated with a poorer outcome.…”

mentioning

confidence: 99%

Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

et al. 2004

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Sarcomas, or tumors of connective tissue, represent roughly 20% of childhood cancers. Although the cure rate for sarcomas in general has significantly improved in the last 10 years, there continue to be subgroups that are difficult to treat. High-grade or metastatic soft-tissue sarcomas and rhabdomyosarcomas (RMS) of the extremities remain therapeutic challenges and their prognosis is often poor. The future of sarcoma therapy will likely include molecular approaches including gene/protein expression profiling and gene-based therapy. Most sarcomas harbor defects in the p53 or pRb pathways. The tumor suppressor p53 is central to regulation of cell growth and tumor suppression and restoring wild-type p53 function in pediatric sarcomas may be of therapeutic benefit. Studies with adenoviral-mediated p53 gene transfer have been conducted in many cancer types including cervical, ovarian, prostatic and head and neck tumors. Studies of this approach, however, remain limited in pediatric cancers, including sarcomas. Using three viral constructs containing cDNA for wild-type p53, mutant p53 (C135S) and lacZ, we studied the effect of adenoviralmediated gene therapy in four pediatric sarcoma cell lines, RD and Rh4 (RMS), Rh1 (Ewing's sarcoma) and A204 (undifferentiated sarcoma). Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, we have shown a dose-dependent decrease in cell viability 72 h post-treatment that occurs with Ad-wtp53 but not with Ad-mutp53. Cells treated with Ad-wtp53 show upregulation of the p53 downstream targets, p21 CIP1/WAF1 and bax. Growth curves demonstrate suppression of cell growth over a period of 4 days and cells treated with Ad-wtp53 demonstrate a significant increase in sensitivity to the chemotherapeutic agents, cisplatin and doxorubicin. Our results indicate that restoration of wild-type p53 function in pediatric sarcoma cells could provide a basis for novel approaches to treatment of this disease.

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“…Transfection of foreign DNA into somatic cells in culture has become an extremely important tool in modem molecular genetics, permitting studies of gene function (7,11,12,31,33), gene regulation (6,8,23,24,30,40,(55)(56)(57), oncogenesis (3,34,36,47,49), and somatic recombination (2, 4, 15, 17, 20, 21, 26, 29, 32, 37, 38, 41, 42, 45, 50-54, 60, 62) that were unimaginable only a few years ago. Despite the usefulness of DNA transfection, very little is known about the pathway by which the biologically active molecules travel from outside the cell into the nucleus or about the status of the DNA once it arrives (19,27).…”

mentioning

confidence: 99%

How damaged is the biologically active subpopulation of transfected DNA?

Wake¹,

Gudewicz²,

Porter³

et al. 1984

Mol. Cell. Biol.

138

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Relatively little is known about the damage suffered by transfected DNA molecules during their journey from outside the cell into the nucleus. To follow selectively the minor subpopulation that completes this journey, we devised a genetic approach using simian virus 40 DNA transfected with DEAE-dextran. We investigated this active subpopulation in three ways: (i) by assaying reciprocal pairs of mutant linear dimers which differed only in the arrangement of two mutant genomes; (ii) by assaying a series of wild-type oligomers which ranged from 1.1 to 2.0 simian virus 40 genomes in length; and (iii) by assaying linear monomers of simian virus 40 which were cleaved within a nonessential region to leave either sticky, blunt, or mismatched ends. We conclude from these studies that transfected DNA molecules in the active subpopulation are moderately damaged by fragmentation and modification of ends. As a whole, the active subpopulation suffers about one break per 5 to 15 kilobases, and about 15 to 20% of the molecules have one or both ends modified. Our analysis of fragmentation is consistent with the random introduction of doublestrand breaks, whose cause and exact nature are unknown. Our analysis of end modification indicated that the most prevalent form of damage involved deletion or addition of less than 25 base pairs. In addition we demonstrated directly that the efficiencies of joining sticky, blunt, or mismatched ends are identical, verifying the apparent ability of cells to join nearly any two DNA ends and suggesting that the efficiency of joining approaches 100%. The design of these experiments ensured that the detected damage preceded viral replication and thus should be common to all DNAs transfected with DEAE-dextran and not specific for viral DNA. These measurements of damage within transfected DNA have important consequences for studies of homologous and nonhomologous recombination in somatic cells as is discussed.Transfection of foreign DNA into somatic cells in culture has become an extremely important tool in modem molecular genetics, permitting studies of gene function

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Oncogenes in solid human tumours

Cited by 449 publications

References 26 publications

Presence of a Kirsten murine sarcoma virus ras oncogene in cells transformed by 3-methylcholanthrene.

Presence of a Kirsten murine sarcoma virus ras oncogene in cells transformed by 3-methylcholanthrene.

Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

How damaged is the biologically active subpopulation of transfected DNA?

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