title: p53-regulated GML gene expression in non-small cell lung cancer. a promising relationship to cisplatin chemosensitivity.
abstract: The GML gene (glycosylphosphatidylinositol-anchored molecule-like protein gene) is a novel gene specifically induced by wild-type p53, which may participate in cell cycle control or the cell apoptotic pathway. Recent experiments suggest that the expression of this novel gene in cancer cells is closely associated with sensitivity to certain anticancer drugs. To elucidate the role of the gene expression in cisplatin (CDDP) chemosensitivity of non-small cell lung cancer (NSCLC), 30 surgically resected materials were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). GML gene expression was detected in 9 (30%) samples. Its incidence was significantly higher in immunohistochemically p53-negative (P=0.040) or wild-type p53 tissues (P=0.041). On in vitro chemosensitivity testing using 29 primary tissues, six samples with GML gene expression showed good sensitivity to CDDP. In particular, in tissues with immunohistochemically p53-negative accumulation, those with GML gene expression showed significantly better in vitro sensitivity to CDDP (P=0.012). Clinically a good response to CDDP-based chemo(thermo)therapy for NSCLC patients with tumour residue or recurrence, was observed only in those with p53-negative accumulation and GML gene expression, in agreement with in vitro results. Thus, although the number of tested samples was small, GML gene expression is commonly detected in immunohistochemically p53-negative NSCLCs in close association with good sensitivity to CDDP. GML gene expression analysis may serve as a predictor of CDDP-based chemotherapy for patients with NSCLC.
authors.affiliation: Department of Thoracic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Nakamichi 1-3-3, Higashirariku, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Higashiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: K
authors.initials: K
authors.lastname: Kodama
authors.forename: H
authors.initials: H
authors.lastname: Yokouchi
authors.forename: K
authors.initials: K
authors.lastname: Takami
authors.forename: M
authors.initials: M
authors.lastname: Nishijima
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: H
authors.initials: H
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Minamigawa
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics*; D018797:Cell Cycle Proteins; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D018365:Neoplasm, Residual / Q000188:drug therapy; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C102519:GML protein, human; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin