Proteomic analysis to dissect mitoxantrone resistance-associated proteins in a squamous lung carcinoma.
BACKGROUND
Mitoxantrone resistance has been related to the expression of a drug efflux pump breast cancer resistance pump (BCRP) but little is known of the intracellular protein changes. In this work, differential protein expression in a squamous lung carcinoma cell line, DLKP, and its mitoxantrone-resistant variant (DLKP-Mitox) was investigated to elucidate other changes associated with mitoxantrone resistance.


METHODS
Differential protein expression between DLKP and DLKP-Mitox was investigated using 2D-DIGE technology. Proteins of interest were identified by MALDI-ToF mass spectrometry. Western blotting was used to confirm and validate some of these changes.


RESULTS
Biological variation analysis in Decyder software revealed a total of 343 proteins to be differentially regulated with p < 0.05. Identification of 61 proteins of interest by mass spectrometry revealed changes in proteins involved in many cellular processes including apoptosis and differentiation.


CONCLUSIONS
Alterations in these cellular processes and proteins present alternative sites to circumvent resistance to mitoxantrone.
Murphy
L
L
National Institute of Cellular Biology, Dublin City University, Ireland.
Clynes
M
M
Keenan
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D000166:Acridines / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008942:Mitoxantrone / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000166:Acridines; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D044005:Tetrahydroisoquinolines; D008942:Mitoxantrone; C083501:Elacridar