Changes in gene expression associated with stable drug and radiation resistance in small cell lung cancer cells are similar to those caused by a single X-ray dose.
Small cell lung cancer (SCLC) initially responds well to chemotherapy and fractionated radiotherapy, but resistance to these treatments eventually develops in the vast majority of cases. To understand how resistance develops in the H69 SCLC cell line, we compared the changes in gene expression associated with 37.5 Gy fractionated X-ray treatment that produced the stable radiation- and drug-resistant H69/R38 cell subline to the changes associated with a single 4- or 8-Gy X-ray treatment. Gene expression was determined by suppression subtractive hybridization combined with Northern blot analysis and two-dimensional (2D) protein electrophoresis. Stable radiation and drug resistance was associated with coordinate changes in the expression of genes of the cytoskeleton, protein synthesis, cell cycle, redox/stress and metabolic pathways. The pattern of these changes was remarkably similar to the changes seen 24 h after a single X-ray treatment of the H69 cells but differed from the changes in expression associated with a single X-ray treatment of the resistant H69/ R38 cells. Stable radiation and drug resistance may be caused by the constitutive expression of those genes transiently expressed by sensitive cells in response to a single X-ray dose. The repeated treatments received during fractionated irradiation may promote the change from a transient to a constitutive pattern of gene expression.
Henness
Sheridan
S
Bill Walsh Cancer Research Laboratories, Royal North Shore Hospital, St Leonards 2065, Australia.
Davey
Mary W
MW
Harvie
Rozelle M
RM
Banyer
Joanne
J
Wasinger
Valerie
V
Corthals
Garry
G
Davey
Ross A
RA
D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D011829:Radiation Dosage; D011836:Radiation Tolerance; D014965:X-Rays
D009363:Neoplasm Proteins