Inheritance of chromosome 7 is associated with a drug-resistant phenotype in somatic cell hybrids.
A major form of drug resistance in tumour cells known as classical multidrug resistance (MDR) is associated with the overexpression of the mdr1 gene product, the membrane protein P-glycoprotein (P-gp), which acts as an energy-dependent drug efflux pump. In this study the inheritance of P-gp expression was examined using hybrids formed after somatic cell fusion between a drug-sensitive human T-cell leukaemia cell line, CEM/CCRF, and a drug-resistant derivative, CEM/A7, which is characterized by a clonal chromosomal duplication dup(7)(q11.23q31.2). Fourteen hybrids, chosen at random, were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR) and by binding studies involving the monoclonal antibody MRK16, which recognises an external P-gp epitope. Only two hybrids were positive for both MRK16 antibody labelling and mdr1 mRNA. Partial karyotypic analysis of all hybrids revealed that only the MRK16-positive hybrids contained the duplication in chromosome 7 seen in the CEM/A7 parental MDR line. Therefore, P-gp overexpression in the MRK16-positive hybrids may be linked to the inheritance of chromosome 7 from CEM/A7 and possibly associated with the chromosome 7 abnormality.
Department of Medical Oncology, Austin & Repatriation Medical Centre, Victoria, Australia.
M
M
de Silva
P
P
Kantharidis
D M
DM
Wall
L
L
Campbell
V
V
Vrazas
G
G
Nadalin
S J
SJ
Kaczmarczyk
X F
XF
Hu
J D
JD
Parkin
J R
JR
Zalcberg
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7; D017931:DNA Primers; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015251:Epirubicin / Q000494:pharmacology; D006801:Humans; D006822:Hybrid Cells; D007945:Leukemia, Lymphoid / Q000235:genetics; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011817:Rabbits; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D017931:DNA Primers; D015251:Epirubicin