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Use of gastrin‐releasing peptide promoter for specific expression of thymidine kinase gene in small‐cell lung carcinoma cells
Author(s) -
Inase Naohiko,
Horita Kouichi,
Tanaka Michiko,
Miyake Shuji,
Ichioka Masahiko,
Yoshizawa Yasuyuki
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000301)85:5<716::aid-ijc19>3.0.co;2-w
Subject(s) - thymidine kinase , gastrin releasing peptide , cell culture , suicide gene , biology , transfection , microbiology and biotechnology , cancer research , hela , transduction (biophysics) , genetic enhancement , gene , herpes simplex virus , virology , virus , bombesin , receptor , biochemistry , genetics , neuropeptide
For specific transduction of herpes simplex virus thymidine kinase (HSV‐tk) into human small‐cell lung carcinoma (SCLC) cells, we explored the 5'‐flanking region (–1.1 kb) of the gastrin‐releasing peptide (GRP) gene as a lung cancer–specific promoter. RT‐PCR analysis demonstrated expression of GRP mRNA in the SBC5 human SCLC cell line but not in the RERF human SCLC cell line, the A549 human lung adenocarcinoma cell line or the HeLa human uterine cervix epithelioid carcinoma cell line. A reporting vector containing the GRP promoter (pGL2‐GRP) exhibited higher luciferase activity in SBC5 than in the other 3 cell lines. After transfecting an expression vector containing the GRP promoter‐bound HSV‐tk gene (pGRP‐TK) into the cells, we measured their sensitivity to ganciclovir (GCV). In SBC5, pGRP‐tk‐transfected cells became about 100 times more sensitive to GCV than parental cells in vitro. In nude mice, tumors of pGRP‐tk‐transfected SBC5 regressed completely after i.p. administration of GCV. GRP promoter might be a good tool for tumor‐specific transduction of suicide genes in GRP‐expressing SCLC cells. Int. J. Cancer 85:716–719, 2000. © 2000 Wiley‐Liss, Inc.