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Effects of an inducible anti‐sense c‐ myc gene transfer in a drug‐resistant human small‐cell‐lung‐carcinoma cell line
Author(s) -
Van Waardenburg Robert C.A.M.,
Meijer Coby,
Burger Herman,
Nooter Kees,
De Vries Elisabeth G.E.,
Mulder Nanno H.,
De Jong Steven
Publication year - 1997
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(19971114)73:4<544::aid-ijc15>3.0.co;2-9
Subject(s) - cell culture , cancer research , gene , lung , carcinoma , cell , sense (electronics) , biology , medicine , pathology , chemistry , genetics
Small‐cell‐lung‐cancer (SCLC) is characterized by rapid development of resistance to cytotoxic agents, such as cisplatin (cDDP) and anthracyclines. c‐ myc over‐expression is one of the reported genetic alterations in this tumor. Amplification of the c‐ myc gene in this and other cancers is often correlated with poor prognosis. We studied the existence of a correlation between resistance and activation of the c‐ myc oncogene in a cDDP‐resistant SCLC sub‐line, GLC 4 cDDP, containing a c‐ myc gene amplification. This cell line was stably transfected with either an anti‐sense c‐myc (AS) or control (C) expression vector resulting in the sub‐clones GLC 4 cDDP/AS and GLC 4 cDDP/C respectively. PCR and RT‐PCR analysis illustrated the integration and activation of the dexamethasone(dex)‐inducible MMTV‐LTR promoter linked to the complete AS‐c‐ myc fragment in GLC 4 cDDP/AS cells, but not in GLC 4 cDDP/C cells. Dex‐induced AS‐c‐ myc RNA resulted in 50% growth inhibition during the first 48 hr, which declined to 25% at 72 hr. In addition, AS‐c‐ myc RNA expression reduced the cloning efficacy by 36% and induced 2‐fold more apoptosis within 24 hr in GLC 4 cDDP/AS cells. Dex treatment did not affect the proliferation, clonogenicity and induction of apoptosis in the control cell lines. Furthermore, AS‐c‐ myc RNA expression caused a 1.4‐fold increased cDDP sensitivity but no change in doxorubicin or vincristine sensitivity in GLC 4 cDDP/AS cells. Our results indicate that AS‐c‐ myc RNA expression causes inhibition of cell proliferation, induces apoptosis, reduces clonogenicity and interferes with cDDP sensitivity but not with doxorubicin or vincristine sensitivity. Int. J. Cancer 73:544–550, 1997. © 1997 Wiley‐Liss, Inc.