Stable transfectants of human MCF-7 breast cancer cells with increased levels of the human folate receptor exhibit an increased sensitivity to antifolates

K. N. Chung, Y. Saikawa, T. H. Paik, K. H. Dixon, T. Mulligan, K. H. Cowan, P. C. Elwood

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

A major problem in cancer therapy is tumor drug resistance such as is found with antifolates (e.g., methotrexate [MTX]). We are specifically interested in the role of the human folate receptor (hFR) in MTX resistance. To investigate whether transfection of hFR results in increased MTX uptake and increased drug sensitivity, human mammary carcinoma (MCF-7) cells and Chinese hamster ovary cells (CHO) (cells which do not express detectable levels of hFR) were transfected with hFR cDNA. Stable human mammary carcinoma and Chinese hamster ovary transfectants expressing high levels of hFR were selected for further analysis. Transfected cells which express increased levels of hFR grow more rapidly than mock transfected or wild type cells in media containing physiologic concentrations of folates. The hFR expressed by these cells is sorted to the plasma membrane and is functional as determined by cell surface binding of a radiolabeled folic acid derivative and by internalization of [3H]methotrexate. The stable transfectants that express increased levels of hFR are also more sensitive to MTX in physiologic concentrations of folates. We conclude that increased expression of hFR by human mammary carcinoma and Chinese hamster ovary cells cultured under these conditions results in an enhanced growth rate, increased folic acid binding, and increased MTX uptake and cytotoxicity.

Original languageEnglish (US)
Pages (from-to)1289-1294
Number of pages6
JournalJournal of Clinical Investigation
Volume91
Issue number4
DOIs
StatePublished - 1993
Externally publishedYes

Keywords

  • cell growth
  • drug resistance
  • folate binding proteins
  • folic acid
  • methotrexate

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Stable transfectants of human MCF-7 breast cancer cells with increased levels of the human folate receptor exhibit an increased sensitivity to antifolates'. Together they form a unique fingerprint.

Cite this