title: Factors involved in the cisplatin resistance of KCP‑4 human epidermoid carcinoma cells.
abstract: KCP-4 is a cisplatin-resistant cell line established from human epidermoid carcinoma KB-3-1 cells. Although our previous study revealed that one of the mechanisms for cisplatin resistance in KCP-4 cells is the activation of NF-κB, its high resistance is considered to be induced by multiple mechanisms. In the present study, we explored other factors involved in the development of cisplatin resistance in KCP-4 cells. Since it has been reported that an unknown efflux pump exports cisplatin from KCP-4 cells in an ATP-dependent manner, we examined 48 types of ATP-binding cassette proteins as candidate cisplatin efflux transporters. The mRNA expression levels of ABCA1, ABCA3, ABCA7 and ABCB10 in KCP-4 cells were higher when compared to those in KB-3-1 cells. These expression levels in cisplatin-sensitive revertant KCP-4 cells (KCP-4R cells), were reduced in parallel with the sensitivity of these cells to cisplatin and their intracellular accumulation of cisplatin. Next, we investigated the occurrence of mutations in p53 in KCP-4 cells. We found a heterozygous missense mutation at codon 72 (p.Pro72Arg) in p53 of both KCP-4 and KB-3-1 cells, but the protein expression level of p53 in KCP-4 cells was higher when compared to that in KB-3-1. These results suggest that ABCA1, ABCA3, ABCA7 and ABCB10 are candidate genes for the cisplatin efflux transporter that is involved in the cisplatin resistance of KCP-4 cells, and that the mutation at codon 72 of p53 may contribute to the development of cisplatin resistance.
authors: Department of Pharmaceutical Health Care Sciences, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.
authors: Shigeru
authors: S
authors: Oiso
authors: Department of Pharmaceutical Health Care Sciences, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.
authors: Yui
authors: Y
authors: Takayama
authors: Department of Pharmaceutical Health Care Sciences, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.
authors: Rie
authors: R
authors: Nakazaki
authors: Department of Pharmaceutical Health Care Sciences, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.
authors: Naoko
authors: N
authors: Matsunaga
authors: Department of Pharmaceutical Health Care Sciences, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.
authors: Chie
authors: C
authors: Motooka
authors: Department of Pharmaceutical Health Care Sciences, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.
authors: Asuka
authors: A
authors: Yamamura
authors: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890‑8520, Japan.
authors: Ryuji
authors: R
authors: Ikeda
authors: Department of Biopharmaceutics, Nihon Pharmaceutical University, Saitama 362-0806, Japan.
authors: Kazuo
authors: K
authors: Nakamura
authors: Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890‑8520, Japan.
authors: Yasuo
authors: Y
authors: Takeda
authors: Department of Pharmaceutical Health Care Sciences, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.
authors: Hiroko
authors: H
authors: Kariyazono
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004789:Enzyme Activation; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D002945:Cisplatin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C577836:ABCA1 protein, human; C441524:ABCA3 protein, human; C411895:ABCA7 protein, human; C412459:ABCB10 protein, human