TY - JOUR
T1 - Genomic instability in drug-resistant human melanoma cell lines detected by Alu-I-arbitrary-primed PCR
AU - Brkic, Gordana
AU - Gopas, Jacob
AU - Tanic, Nicola
AU - Dedovic-Tanic, Nasta
AU - Benharroch, Daniel
AU - Finkelstein-Jaworowsky, Eve
AU - Kedar, Igar
AU - Dimitrijevic, Bogomir
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Destabilization of the genome seems to be an important step in the generation of drug resistance. Since malignant melanoma is extremely resistant to chemotherapy, we used human melanoma cell lines as a model to investigate the putative role of genomic instability in the appearance of drug resistance. Drug-resistant variants were obtained with MNNG, BiCNU, doxorubicin and 6-thioguanine selection of melanoma cell lines. Genomic alterations in variant cells were detected by arbitrarily primed PCR of Alu-I digested DNA (AIu-I-AP-PCR). Two differential DNA bands from 6-TG-resistant cell variants were sequenced. One is homologous to intron 25 of the neural cell adhesion molecule L1 and the second to endogenous retroviral LTR sequences. We have shown that drug-resistant melanoma cell lines accumulate genomic alterations that are efficiently detected by Alu I-AP-PCR and that drug-resistant variants show genomic instability, including variations in LTR sequences, which may be associated with the appearance of the drug resistance phenotype.
AB - Destabilization of the genome seems to be an important step in the generation of drug resistance. Since malignant melanoma is extremely resistant to chemotherapy, we used human melanoma cell lines as a model to investigate the putative role of genomic instability in the appearance of drug resistance. Drug-resistant variants were obtained with MNNG, BiCNU, doxorubicin and 6-thioguanine selection of melanoma cell lines. Genomic alterations in variant cells were detected by arbitrarily primed PCR of Alu-I digested DNA (AIu-I-AP-PCR). Two differential DNA bands from 6-TG-resistant cell variants were sequenced. One is homologous to intron 25 of the neural cell adhesion molecule L1 and the second to endogenous retroviral LTR sequences. We have shown that drug-resistant melanoma cell lines accumulate genomic alterations that are efficiently detected by Alu I-AP-PCR and that drug-resistant variants show genomic instability, including variations in LTR sequences, which may be associated with the appearance of the drug resistance phenotype.
KW - Alu-I-arbitrary-primed PCR (Alu-IAP-PCR)
KW - Genomic instability
KW - Melanoma
KW - Retroviral LTR sequences
UR - http://www.scopus.com/inward/record.url?scp=0042306459&partnerID=8YFLogxK
M3 - Article
C2 - 12894547
AN - SCOPUS:0042306459
SN - 0250-7005
VL - 23
SP - 2601
EP - 2608
JO - Anticancer Research
JF - Anticancer Research
IS - 3 B
ER -
