Cellular models of drug- and radiation-resistant small cell lung cancer.
BACKGROUND
The H69-EPR, H69-CP, H69-VP and H69/R38 resistant sublines of the classic small cell lung cancer (SCLC) line have proven useful in studies of resistance and its circumvention with paclitaxel.


METHODS
The suppressor/oncogene profile of these sublines determined by Western and Northern blot was compared to the variant H82 SCLC cell profile. Two-dimensional electrophoresis/mass spectrometry was used to determine the effect of paclitaxel on protein expression.


RESULTS
The H69-EPR and H69-CP resistant sublines were similar to the variant H82 cells for bcl-2, p21waf1, p53, N-myc and c-myc expression while the H69-VP subline retained the classic H69 pattern. A 1-h treatment with 10 ng/ml paclitaxel substantially reversed the resistance except for the H69/R38 subline and tended to reverse the resistance-associated changes in protein expression in the H69-EPR subline.


CONCLUSIONS
Although some resistant sublines express a variant pattern of suppressor/oncogenes with low bcl-2, resistance is substantially reversed by paclitaxel treatment.
Davey
Ross A
RA
Bill Walsh Cancer Research Laboratories, Royal North Shore Hospital, St Leonards NSW 2065, Australia. rdavey@med.usyd.edu.au
Locke
Vicki L
VL
Henness
Sheridan
S
Harvie
Rozelle M
RM
Davey
Mary W
MW
D000972:Antineoplastic Agents, Phytogenic; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D017239:Paclitaxel / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D000972:Antineoplastic Agents, Phytogenic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel