Abstract
As a first step towards elucidating the potential role(s) of bcl-2 and bcl-2-related genes in lung tumorigenesis and therapeutic responsiveness, the expression of these genes has been examined in a panel of lung cancer cell lines derived from untreated and treated patients, and in cell lines selected in vitro for multidrug resistance. Bcl-2 was hyperexpressed in 15 of 16 small-cell lung cancer (SCLC) cell lines and two of five non-small-cell lung cancer (NSCLC) lines compared with normal lung and brain, and hyperexpression was not chemotherapy related. Bcl-x was hyperexpressed in the majority of SCLC and NSCLC cell lines as compared with normal tissues, and all lung tumour lines preferentially expressed bcl-x1-mRNA, the splice variant form that inhibits apoptosis. Bax gene transcripts were hyperexpressed in most SCLC and NSCLC cell lines examined compared with normal adult tissues. Mutant p53 gene expression was detected in the majority of the cell lines and no relationship between p53 gene expression and the expression of either bcl-2, bcl-x or bax was observed. No changes in bcl-2, bcl-x and bax gene expression were observed in multidrug-resistant cell lines compared with their drug-sensitive counterparts.
Highlights
As a first step towards investigating the possible involvement of bcl-2, bcl-x, and bax in lung tumour development and the roles played by these genes in determining therapeutic responsiveness, the present study investigates the expression of bcl-2, bcl-x and bax together with p53 in small-cell lung cancer (SCLC) cell lines derived from untreated and pretreated patients, in non-small-cell lung cancer (NSCLC) cell lines and in SCLC and NSCLC cell lines selected in vitro for multidrug resistance
It can be seen that the bcl-2 cDNA probe detected a 8.5 kb transcript in all SCLC cell lines examined with the exception of COR-L279
It can be seen that all SCLC cell lines examined hyperexpressed the bcl-2 gene as compared with normal adult human brain and lung
Summary
With the exception of NCI-H69 (donated by Drs D Carney and A Gazdar, National Cancer Institute Navy Medical Oncology Branch, Bethesda, MD, USA) and LUDLU-1 (supplied by Dr P H Rabbitts of this unit), all lung tumour cell lines used in this study were generous gifts from Dr P R Twentyman (of this unit). The derivation and characterisation of the cell lines COR-L24, -L42, -L47,-L51, -L88 and L23, have been described previously (Baillie-Johnson et al, 1985). Cell lines COR-L51, -L88, -L103, -L311, L316 and -L321 were derived from SCLC patients receiving combination chemotherapy including etoposide, vincristine, methotrexate and cycloheximide. The derivation and characterisation of the multidrug-resistant variants of NCI-H69, MOR and COR-L23 are described in detail elsewhere (Twentyman et al, 1986). All cell lines were routinely grown in RPMI-1640 medium supplemented with 2 mM L-glutamine, 10% fetal calf serum (FCS), 10 ,ug ml-1 penicillin and 10 jug ml-' streptomycin (all Gibco BRL, Paisley, UK) with the exception that DoHH2 was grown in RPMI-1640 supplemented with 5% FCS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
