Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosoma haematobium infection

作者：Ma Ning; Thanan Raynoo; Kobayashi Hatasu; Hammam Olfat; Wishahi Mohamed; El Leithy Tarek; Hiraku Yusuke; Amro El Karef; Oikawa Shinji; Ohnishi Shiho; Murata Mariko; Kawanishi Shosuke^*

来源：Biochemical and Biophysical Research Communications, 2011, 414(2): 344-349.

DOI：10.1016/j.bbrc.2011.09.073

• Bladder cancer
• Stem cells
• Oct3/4
• Nitrative DNA damage
• iNOS
• Inflammation

To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosoma haematobium (S. haematobium). We also detected the expression of nuclear factor-kappa B (NF-kappa B) and inducible nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-kappa B in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stern cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S. haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-kappa B activation, leading to tumor development.

• 出版日期2011-10-22