Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA

Mol Cell Biol. 1987 Dec;7(12):4549-52. doi: 10.1128/mcb.7.12.4549-4552.1987.

Abstract

Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the level of transcription without a corresponding loss of amplified DNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA, Neoplasm / metabolism*
  • Doxorubicin / pharmacology
  • Drug Resistance / genetics*
  • Gene Amplification*
  • Gene Expression Regulation*
  • Humans
  • Leukemia, Myeloid / genetics*
  • Nucleic Acid Hybridization
  • RNA, Messenger / genetics
  • Tumor Cells, Cultured
  • Vincristine / pharmacology

Substances

  • DNA, Neoplasm
  • RNA, Messenger
  • Vincristine
  • Doxorubicin