| Popis: |
The purpose of this grant is to understand how activation of the NF-KB/Rel family of transcription factors leads to breast cancer cell survival following treatment with radiation. The NF-kB/Rel family of transcription factors are known to greatly affect survival of various cancer cell types, including breast cancer cells. Our hypothesis is that activation of NF-icB in breast cancer cells contributes to a G2/M cell cycle arrest, affording these cell extra opportunity to repair damaged DNA and thus allowing them to evade death inducing effects of radiation. Cell cycle analysis and levels of apoptosis were determined following exposure to ionizing irradiation. Cells capable of NF-xB activation efficiently arrested in G2/M cell cycle phase while those that are not capable of activating NF-icB, do not efficiently arrest. Using RPA analysis, we identified a gene, p21(wafl1/Cipl1), and have now shown that it is involved in maintaining the G2/M phase cell cycle arrest following IR. Through the use of stable RNAi interference, we found that the G2/M arrest is partially dependent on p21(wafl/Cipl). Understanding how NF-icB is activated and how NF-KB provides protection from cell death will be important for designing strategies to circumvent this resistance mechanism to improve efficacy of radiation therapy. |
