Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) correlates with cisplatin resistance in human non-small cell lung cancer xenografts.
Copper-transporting P-type adenosine triphosphatase (ATP7B) is reportedly associated with platinum drug resistance in various solid carcinomas. However, the impact of ATP7B on platinum drug resistance in non-small cell lung cancer (NSCLC) remains unknown. We investigated ATP7B expression in nine human NSCLC xenografts using real-time polymerase chain reaction (PCR) and immunohistochemistry, and examined the relationship between the expression level of ATP7B and in vivo cisplatin (CDDP) sensitivity. ATP7B mRNA expression was significantly correlated with in vivo cisplatin sensitivity [coefficient of determination (R(2))=0.949, p=0.005]. ATP7B protein was detected in the nine xenografts. The ATP7B protein expression level was comparable to that of ATP7B mRNA. ATP7B mRNA and protein expression levels in the CDDP-resistant xenografts were significantly higher than those in the CDDP-sensitive xenografts (p=0.0389 and p=0.0357, respectively, Mann-Whitney U test). These results suggest that ATP7B is a CDDP-resistance marker in human NSCLC xenografts in vivo.
Nakagawa
Tomoki
T
Department of General Thoracic Surgery, Tokai University School of Medicine, Kanagawa 259-1193, Japan.
Inoue
Yoshimasa
Y
Kodama
Hiroko
H
Yamazaki
Hitoshi
H
Kawai
Kenji
K
Suemizu
Hiroshi
H
Masuda
Ryota
R
Iwazaki
Masayuki
M
Yamada
Shunsuke
S
Ueyama
Yoshito
Y
Inoue
Hiroshi
H
Nakamura
Masato
M
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002945:Cisplatin / Q000627:therapeutic use*; D000073840:Copper-Transporting ATPases; D019008:Drug Resistance, Neoplasm; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D012333:RNA, Messenger; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D002945:Cisplatin