http://hdl.handle.net/2144/2708 2013-05-23T22:58:20Z 2013-05-23T22:58:20Z Yaar, Mina Eller, Mark S Panova, Izabela Kubera, John Wee, Lee Hng Cowan, Kenneth H Gilchrest, Barbara A http://hdl.handle.net/2144/3305 2012-01-12T07:00:45Z 2007-01-26T00:00:00Z

Telomeric DNA Induces Apoptosis and Senescence of Human Breast Carcinoma Cells Yaar, Mina; Eller, Mark S; Panova, Izabela; Kubera, John; Wee, Lee Hng; Cowan, Kenneth H; Gilchrest, Barbara A INTRODUCTION. Cancer is a leading cause of death in Americans. We have identified an inducible cancer avoidance mechanism in cells that reduces mutation rate, reduces and delays carcinogenesis after carcinogen exposure, and induces apoptosis and/or senescence of already transformed cells by simultaneously activating multiple overlapping and redundant DNA damage response pathways. METHODS. The human breast carcinoma cell line MCF-7, the adriamycin-resistant MCF-7 (Adr/MCF-7) cell line, as well as normal human mammary epithelial (NME) cells were treated with DNA oligonucleotides homologous to the telomere 3' overhang (T-oligos). SCID mice received intravenous injections of MCF-7 cells followed by intravenous administration of T-oligos. RESULTS. Acting through ataxia telangiectasia mutated (ATM) and its downstream effectors, T-oligos induced apoptosis and senescence of MCF-7 cells but not NME cells, in which these signaling pathways were induced to a far lesser extent. In MCF-7 cells, experimental telomere loop disruption caused identical responses, consistent with the hypothesis that T-oligos act by mimicking telomere overhang exposure. In vivo, T-oligos greatly prolonged survival of SCID mice following intravenous injection of human breast carcinoma cells. CONCLUSION. By inducing DNA damage-like responses in MCF-7 cells, T-oligos provide insight into innate cancer avoidance mechanisms and may offer a novel approach to treatment of breast cancer and other malignancies.

2007-01-26T00:00:00Z Byles, Vanessa Chmilewski, Laura K. Wang, Joyce Zhu, Lijia Forman, Lora W. Faller, Douglas V. Dai, Yan http://hdl.handle.net/2144/2918 2012-01-10T07:00:21Z 2010-10-07T00:00:00Z

Aberrant Cytoplasm Localization and Protein Stability of SIRT1 is Regulated by PI3K/IGF-1R Signaling in Human Cancer Cells Byles, Vanessa; Chmilewski, Laura K.; Wang, Joyce; Zhu, Lijia; Forman, Lora W.; Faller, Douglas V.; Dai, Yan SIRT1, an NAD-dependent histone/protein deacetylase, has classically been thought of as a nuclear protein. In this study, we demonstrate that SIRT1 is mainly localized in the nucleus of normal cells, but is predominantly localized in the cytoplasm of the cancer / transformed cells we tested. We found this predominant cytoplasmic localization of SIRT1 is regulated by elevated mitotic activity and PI3K/IGF-1R signaling in cancer cells. We show that aberrant cytoplasmic localization of SIRT1 is due to increased protein stability and is regulated by PI3K/IGF-1R signaling. In addition, we determined that SIRT1 is required for PI3K-mediated cancer cell growth. Our study represents the first identification that aberrant cytoplasm localization is one of the specific alternations to SIRT1 that occur in cancer cells, and PI3K/IGF-1R signaling plays an important role in the regulation of cytoplasmic SIRT1 stability. Our findings suggest that the over-expressed cytoplasmic SIRT1 in cancer cells may greatly contribute to its cancer-specific function by working downstream of the PI3K/IGF-1R signaling pathway.

2010-10-07T00:00:00Z Koh, H K http://hdl.handle.net/2144/2831 2012-01-10T07:01:51Z 1995-11-01T00:00:00Z

Preventive Strategies and Research for Ultraviolet-Associated Cancer Koh, H K Ultraviolet (UV)-associated cancer is the most common cancer in the United States. Approximately 90% of nonmelanoma skin cancer and 65% of melanoma are attributable to UV exposure and theoretically could be eliminated by primary prevention measures. Safe sun strategy includes use of sunscreens, use of protective clothing, minimization of exposure from 10 A.M. to 3 P.M., and avoidance of tanning parlors. Although more definitive data in human populations on the effectiveness of sunscreens to prevent melanoma and skin cancer are needed, sunscreens are thought to reduce risk. Safe sun prevention must start in childhood and adolescence when people receive most of their UV exposure. Secondary prevention through professional and public education and early detection may further reduce melanoma mortality.

1995-11-01T00:00:00Z