title: p300 mediates cellular resistance to doxorubicin in bladder cancer.
abstract: Bladder cancer is one of the most common urogenital malignancies. At the non-invasive stage, bladder cancer can be completely resected transurethrally. However, 70% of patients experience intravesical tumor recurrence within 5 years. Patients with advanced bladder cancer frequently receive a chemotherapy regimen containing doxorubicin. However, doxorubicin resistance is a major obstacle to cancer chemotherapy. Previously, we reported that the histone acetyltransferase p300/CBP-associated factor is involved in doxorubicin resistance in bladder cancer. However, the role of another histone acetyltransferase, p300, in bladder cancer resistance to doxorubicin remains unclear. In this study, we investigated the molecular mechanism of doxorubicin resistance in bladder cancer with regard to p300. The result showed that p300 expression was reduced in doxorubicin-resistant bladder cancer cells and in response to doxorubicin exposure. Furthermore, p300 suppression rendered bladder cancer cells resistant to doxorubicin. Taken together, the results from this study indicate that p300 may be a promising molecular therapeutic target through the modulation of cellular sensitivity to doxorubicin in bladder cancer.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu                     University, Fukuoka 812-8582, Japan.
authors.forename: Ario
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tatsugami
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.forename: Shingo
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kuroiwa
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Eto
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D001749:Urinary Bladder Neoplasms
chemical_list: D000903:Antibiotics, Antineoplastic; D034741:RNA, Small Interfering; D004317:Doxorubicin; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human