[Study on the genetic alterations in MTX-resistant cells by differential polymerase chain reaction].
Gene amplification is a common mechanism that contributes to the drug resistance. To explore the molecular genetic background related to the MTX resistance in the mouse MTX-resistant cells, differential PCR was used to determine the amplification and overexpression of DHFR gene. In addition, the correlations between c-myc, p53 status and dhfr amplification were studied. Amplification and overexpression of dhfr suggested its role in MTX-resistant cells. However, no amplification and overexpression of c-myc were detected. On the other hand, no alteration of p53 copy number was found. The increased mRNA level of p53 suggested the normal function of p53. These results implicated the status of c-myc and p53 had no correlation with dhfr amplification, therefore some other molecular genetic alterations may exist to permit the dhfr amplification in MTX-resistant cells.
Zhang
Yu
Y
Laboratory of Medical Genetics, Harbin Medical University, Harbin 150086, China. zhangyu@yahoo.com.cn
Deng
Xin-Yu
XY
Zhang
Xiao-Ling
XL
Zhang
Gui-Yin
GY
Li
Pu
P
Fu
Song-Bin
SB
D000818:Animals; D004351:Drug Resistance; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells; D016133:Polymerase Chain Reaction / Q000379:methods*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate