title: Heat shock protein 72 does not modulate ionizing radiation-induced apoptosis in U1810 non-small cell lung carcinoma cells.
abstract: Heat shock proteins (HSP) have been shown to interfere with apoptosis signaling, suggesting that there might be a role for these proteins as mediators of resistance to ionizing radiation (IR)-induced apoptosis. Protein expression of the stress inducible heat shock proteins, HSP72 and HSP27, was analyzed in a panel of lung carcinoma cell lines displaying various degrees of radiosensitivity. Expression of HSP72 was high in all cell lines investigated while HSP27 was present in all non-small cell lung carcinoma (NSCLC) and 6/9 small cell lung carcinoma (SCLC) cell lines. Heat shock, but not IR, induced or further increased the expression of HSP27 and HSP72. Moreover, elevation of heat shock protein level prior to irradiation did not attenuate IR-induced apoptotic signaling or the induction of apoptosis. Protein level of HSP72 was downregulated in a radioresistant NSCLC cell line by RNA interference. However, this did not sensitize cells to treatment with DNA-damaging agents such as IR, cisplatin or VP16. Thus, the results from this first study on the relationship between stress-inducible HSP expression and IR-induced apoptosis in lung cancer cells do not support a role for HSP 27 and 72 in the radioresistance of NSCLC cells.
authors.affiliation: Institute of Environmental Medicine, Department of Toxicology, Unit of Medical Radiobiology, Cancercentrum Karolinska, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ekedahl
authors.forename: Bertrand
authors.initials: B
authors.lastname: Joseph
authors.forename: Philippe
authors.initials: P
authors.lastname: Marchetti
authors.forename: Harold
authors.initials: H
authors.lastname: Fauvel
authors.forename: Pierre
authors.initials: P
authors.lastname: Formstecher
authors.forename: Rolf
authors.initials: R
authors.lastname: Lewensohn
authors.forename: Boris
authors.initials: B
authors.lastname: Zhivotovsky
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D005047:Etoposide / Q000494:pharmacology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000502:physiology*; D006358:Hot Temperature; D006801:Humans; D019169:Jurkat Cells; D008175:Lung Neoplasms; D011506:Proteins / Q000032:analysis; D034741:RNA, Small Interfering; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
chemical_list: D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011506:Proteins; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; D005047:Etoposide; D020169:Caspases; D002945:Cisplatin