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Archive - Mar 20, 2010

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Differences in Transcription Factor Binding May Explain Many Human Differences

Differences in gene expression associated with differences in transcription factor binding may help explain many of the differences among individual humans, according to a team of Yale University researchers and collaborators. Transcription factors bind to DNA regions and set in motion programs of increased or decreased gene expression through their influence on the binding of RNA polymerase and the transcription of DNA to RNA. Using the technique of chromatin immunoprecipitation followed by sequencing (ChIP-Seq), the authors showed, on a genome wide basis, that the binding regions for RNA polymerase II and NF-kappa B differed by 25 percent and 7.5 percent, respectively, between any two human individuals in samples of lymphoblastoid cells from 10 individuals of various ancestries. RNA polymerase II, which is active in all cells, transcribes DNA into RNA, and its activity is dependent on the appropriate transcription factors being present at the DNA binding regions. NF-kappa B is a transcription factor that is activated by stress, plays a key role in immune responses to infections, and has been implicated in several diseases, including cancer. Approximately 19,000 and 15,500 binding regions were found for RNA polymerase II and NF-kappa B, respectively, in the study. The researchers found that differences in the binding of RNA polymerase II and NF-kappa B at DNA regions were frequently associated with SNPs and genomic structural variants (SVs), such as duplications, deletions, and inversions of long stretches of DNA, and were often correlated with differences in gene expression, suggesting functional consequences of binding variation.

Cough Medicine Ingredient Shows Promise for Prostate Cancer Treatment

Researchers have shown that, in mice, the cough medicine ingredient noscapine inhibits prostate tumor growth and also limits the spread of tumors without causing any side-effects. Noscapine, a non-addictive derivative of opium, has been used worldwide since the 1950s as an ingredient in over-the-counter cough medicines and was originally suggested as an anti-cancer agent in the early 1960s--but major studies of its anti-cancer properties have only taken place in recent years. The current research focused on pre-treating mice with noscapine before injecting them with prostate cancer cells. This resulted in the tumor growth rate being two-thirds lower in the noscapine group than in a non-noscapine group. The study also found that metastasis rates to the lung were 80 percent lower in the mice pre-treated with noscapine. The scientists further noted that the noscapine group suffered no cancer-related weight loss--compared with significant weight loss in the non-noscapine group. They concluded that noscapine administered as a preventive measure may offer significant benefits in the management of prostate cancer, a disease that kills more than 28,000 men in the U.S. each year. The research team is now hoping to further its efforts by examining the effects of noscapine as a prophylactic agent given to patients following prostate cancer surgery or radiation. "Based on our research so far, we believe that noscapine could be a very promising treatment to prevent recurrence in such cases due to its excellent safety record and oral bioavailability," said co-author Dr. Israel Barker, Founder and Medical Director of the Prostate Cancer Research and Education Foundation. This new pre-clinical research was reported in Volume 30(2) of Anticancer Research.