title: The modifier subunit of glutamate cysteine ligase relates to cisplatin resistance in human small cell lung cancer xenografts in vivo.
abstract: Glutamate cysteine ligase (GCL) plays an important role in the intracellular detoxification of cisplatin (CDDP). GCL is composed of a modifier or light chain subunit (GCLM) and a catalytic or heavy chain subunit (GCLC). Previously, we showed that the GCL subunits enhanced CDDP-resistance in non-small cell lung cancer (NSCLC) xenografts. In small cell lung cancer (SCLC), it is unclear whether the GCL subunits are essential to CDDP-resistance. We examined the gene expression of GCLM and GCLC in four human SCLC xenografts with the real-time polymerase chain reaction (PCR). An in vivo drug sensitivity test with CDDP was performed on the SCLC xenografts. CDDP-resistance was examined as the growth ratio of the relative volume of the treated xenografts to the controls (T/C%). The expression level of GCLM gene in SCLC was significantly lower than that in NSCLC (p=0.0026, Welch's t-test). One of four SCLC xenografts showed 62% of T/C and this was evaluated as CDDP-resistance, while the other three xenografts were sensitive to CDDP in vivo (Mann-Whitney U-test, p<0.01, one-sided). The expression level of the GCLM gene was significantly correlated to T/C% (Fisher's test, p=0.0289, correlations = 0.975), while the GCLC gene expression level was not associated with T/C%. These results suggest that the overexpression of GCLM is correlated with CDDP-resistance in SCLC xenografts in vivo.
authors: Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
authors: Masatake
authors: M
authors: Nishi
authors: Yoshiyuki
authors: Y
authors: Abe
authors: Sakashi
authors: S
authors: Fujimori
authors: Atsushi
authors: A
authors: Hamamoto
authors: Yoshimasa
authors: Y
authors: Inoue
authors: Noriyuki
authors: N
authors: Miyazaki
authors: Yasuhisa
authors: Y
authors: Oida
authors: Norihiro
authors: N
authors: Ikoma
authors: Yasuyuki
authors: Y
authors: Ohnishi
authors: Hitoshi
authors: H
authors: Yamazaki
authors: Yoshito
authors: Y
authors: Ueyama
authors: Masato
authors: M
authors: Nakamura
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D021122:Protein Subunits / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D021122:Protein Subunits; D012333:RNA, Messenger; D005721:Glutamate-Cysteine Ligase; D002945:Cisplatin