Cancer cells (Cold Spring Harbor, N.Y. : 1989)最新文献

The quest for methods to protect cells from the damaging effects of ionizing radiation led to the observation that cytokines, endogenously produced hormone-like polypeptides, are radioprotective. Interleukin-1 and tumor necrosis factor-alpha, given before irradiation, can protect mice from doses of radiation that would be fatal to untreated animals. At lower doses of radiation, the hemopoietic growth factors, interleukin-1, interleukin-4, interleukin-6, tumor necrosis factor-alpha, interferon, and leukemia inhibitory factor can promote recovery when administered after irradiation. Exposure to ionizing radiation selectively induces expression of some cytokines. Recent work suggests that certain cytokines may initiate autocrine/paracrine regulated recovery and repair pathways. Thus, the radioprotective and therapeutic effects of supplementary pharmacological doses of cytokines may act by amplifying innate defenses to ionizing radiation.

An imbalance of DNA methylation, involving widespread hypomethylation, regional hypermethylation and increased cellular capacity for methylation, is characteristic of human neoplasia. This imbalance begins in preneoplastic cells and becomes more extensive throughout subsequent stages of tumor progression. In normal cells, a primary function of DNA methylation may be to modulate compartmentalization of DNA to ensure that regional areas of transcriptionally active chromatin replicate earlier than the bulk transcriptionally inactive chromatin. We argue here that the altered methylation patterns observed during tumor progression, especially regional hypermethylation, may mark--or even help to establish--abnormalities of chromatin organization. In turn, these changes in chromatin structure may, through direct transcriptional inactivation of genes, predisposition to mutations, and allelic deletions, mediate the progressive losses of gene expression associated with tumor development.

Association of ras protein with the plasma membrane is critical for its transforming activity. This association is promoted by a series of post-translational modifications that are signaled by the consensus C-terminal CAAX motif present in all ras proteins. The recent discovery that a 15-carbon isoprenoid (farnesyl) group, derived from an essential intermediate in cholesterol biosynthesis, is attached covalently to ras proteins has stimulated considerable interest and has suggested several important new directions for ras studies. In particular, one promising pharmacologic approach for antagonizing oncogenic ras activity in human malignancies would be to design specific inhibitors of the enzymes that catalyze ras processing and thereby interfere with ras protein association with the plasma membrane.

For many scientists it is often difficult to predict which meetings, among the plethora convening each year, will be the most rewarding. A particular strength of the Zülch symposium was the lively exchange of novel findings and ideas among researchers tackling problems as diverse as photoreceptor cell development in Drosophila and the molecular basis of tumor metastasis. It is these small focused meetings which draw together molecular biologists, clinicians, and pathologists that bear the key to success. Both of us felt strongly that all participants took ideas back home. What else could we ask for? If Zülch had been granted the opportunity to come to Goslar, he would have enjoyed this symposium very much.

DNA-PK is a moderately abundant serine/threonine protein kinase found in the nucleus of a wide range of eukaryotic cells. It is one of the few known cellular enzymes whose activity is regulated directly by DNA. Many DNA binding proteins, including a number of transcription factors, are substrates for DNA-PK in vitro. We suggest that this kinase may coordinate signal transduction pathways and nuclear events, including transcription, in response to changes in DNA or chromatin state.