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M. K. Krevosky, A. E. Galanis, J. A. Bowen, E. A. Whiston, N. Sugi, M. Gregory, B. R. Ksander; Does B-crystallin Mediate Chemoresistance in Retinoblastoma?. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5932.
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The small heat shock protein B-crystallin inhibits apoptosis induced by diverse stimuli through inhibition of caspase-3. We previously demonstrated that B-crystallin is expressed in the retina and is important in blocking retinal apoptosis triggered during destructive endophthalmitis. In addition to being a critical factor in protecting the retina, B-crystallin has additional functions outside of the eye. In diverse tumor cells, B-crystallin was shown to confer resistance to chemotherapy. The ocular tumor retinoblastoma (Rb) presents with a wide range of sensitivity to chemotherapy and we hypothesize that B-crystallin is expressed in Rb tumors that are resistant to chemotherapy and not expressed in those that are susceptible to treatment. Methods &
Paraffin sections from fifteen Rb tumor-containing eyes were examined by IHC. Of 15 Rb sections examined, 12 (80%) expressed B-crystallin, indicating B-crystallin is frequently expressed in Rb. In order to determine whether B-crystallin inhibits apoptosis in Rb cells treated with chemotherapeutic agents, three Rb cell lines (Rb116, Rb125 and Rb143) were analyzed by Western blot and IHC for B-crystallin. One primary cell line (Rb125) expressed B-crystallin, while B-crystallin was not detected in either Rb116 or Rb143. In order to determine the role of B-crystallin in the sensitivity of these Rb cell lines to chemotherapeutic treatment, B-crystallin is being downregulated in Rb125 via siRNA, while Rb116 and Rb143 are being transfected with the cDNA for B-crystallin. These tumor cell lines will be selected and tested for their sensitivity to chemotherapeutic treatment, thereby allowing us to directly address whether B-crystallin confers chemoresistance in Rb tumor cells.
There is a wide range in the sensitivity of Rb tumors to treatment with chemotherapy. Defining the mechanisms of resistance will provide new therapeutic targets for clinically difficult cases. If linked to chemoresistance, B-crystallin can be downregulated within the tumor prior to treatment, increasing the response of the tumor to treatment.
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