Details

Autor(en) / Beteiligte

• Tanida, Satoshi
• Mizoshita, Tsutomu
• Ozeki, Keiji
• Tsukamoto, Hironobu
• Kamiya, Takeshi
• Kataoka, Hiromi
• Sakamuro, Daitoku
• Joh, Takashi
• Bencini, Lapo

Titel

Mechanisms of Cisplatin-Induced Apoptosis and of Cisplatin Sensitivity: Potential of BIN1 to Act as a Potent Predictor of Cisplatin Sensitivity in Gastric Cancer Treatment

Ist Teil von

• International Journal of Surgical Oncology, 2012-01, Vol.2012, p.862879-8

Ort / Verlag

United States: Hindawi Limiteds

Erscheinungsjahr

2012

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Cisplatin is the most important and efficacious chemotherapeutic agent for the treatment of advanced gastric cancer. Cisplatin forms inter- and intrastrand crosslinked DNA adducts and its cytotoxicity is mediated by propagation of DNA damage recognition signals to downstream pathways involving ATR, p53, p73, and mitogen-activated protein kinases, ultimately resulting in apoptosis. Cisplatin resistance arises through a multifactorial mechanism involving reduced drug uptake, increased drug inactivation, increased DNA damage repair, and inhibition of transmission of DNA damage recognition signals to the apoptotic pathway. In addition, a new mechanism has recently been revealed, in which the oncoprotein c-Myc suppresses bridging integrator 1 (BIN1), thereby releasing poly(ADP-ribose)polymerase 1, which results in increased DNA repair activity and allows cancer cells to acquire cisplatin resistance. The present paper focuses on the molecular mechanisms of cisplatin-induced apoptosis and of cisplatin resistance, in particular on the involvement of BIN1 in the maintenance of cisplatin sensitivity.