Cisplatin-Induced Renal Injury Is Independently Mediated by OCT2 and p53

• Published in: Clinical cancer research Vol. 20; no. 15; pp. 4026 - 4035
• Main Authors: SPROWL, Jason A, LANCASTER, Cynthia S, CIARIMBOLI, Giuliano, SPARREBOOM, Alex, PABLA, Navjotsingh, HERMANN, Edwin, KOSLOSKE, Ashley M, GIBSON, Alice A, LIE LI, ZEEH, Dorothea, SCHLATTER, Eberhard, JANKE, Laura J
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.2014
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - metabolism; Antineoplastic Agents - toxicity; Benzothiazoles - pharmacology; Biological and medical sciences; Biomarkers - metabolism; Cisplatin - metabolism; Cisplatin - toxicity; Female; Gene Expression Profiling; Homeodomain Proteins - metabolism; Kidney Diseases - chemically induced; Kidney Diseases - pathology; Kidney Diseases - prevention & control; Male; Medical sciences; Mice; Mice, Knockout; Octamer Transcription Factor-1 - antagonists & inhibitors; Octamer Transcription Factor-1 - physiology; Oligonucleotide Array Sequence Analysis; Organic Cation Transport Proteins - antagonists & inhibitors; Organic Cation Transport Proteins - physiology; Organic Cation Transporter 2; Pharmacology. Drug treatments; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Toluene - analogs & derivatives; Toluene - pharmacology; Tumor Suppressor Protein p53 - antagonists & inhibitors; Tumor Suppressor Protein p53 - physiology; Antineoplastic agent; Alkylating agent; TP53 Gene; Urinary system; Toxicity; Transcription factor Oct2; Cisplatin; Kidney; Platinum II Complexes; Tumor suppressor gene

Tubular secretion of cisplatin is abolished in mice deficient for the organic cation transporters Oct1 and Oct2 (Oct1/2(-/-)mice), and these animals are protected from severe cisplatin-induced kidney damage. Since tubular necrosis is not completely absent in Oct1/2(-/-)mice, we hypothesized that alt...