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A tamoxifen resistant cell line (clone 9) has been isolated from the tamoxifen sensitive, hormone responsive MCF-7 breast carcinoma cell line after transfection with mixed cDNA libraries, followed by tamoxifen selection in the presence of oestrogens. Transfection was confirmed by Southern analysis with vector probes. Clone 9 in several-fold more resistant to tamoxifen and other anti-oestrogens than wild type cells when cultured either as a monolayer or as colonies in soft agar but retains oestrogen receptors. Clone 9 was less responsive to 17-beta-oestradiol than were wild type MCF-7. In addition to showing in vitro tamoxifen resistance, clone 9 was also tamoxifen resistant in vivo when xenografted into the nude mouse. Culture medium conditioned by clone 9 cells stimulated quiescent cells of the same clone as well as wild type cells, whereas medium conditioned by wild type MCF-7 was inhibitory to both, suggesting that clone 9 may be secreting an autocrine growth factor. Clone 9 provides a novel model for further investigation of the mechanism of anti-oestrogen resistance that occurs without loss of oestrogen receptors. Preliminary results suggest that an autocrine growth stimulatory mechanism may be one pathway of such resistance.

Original publication

DOI

10.1038/bjc.1993.486

Type

Journal article

Journal

Br J Cancer

Publication Date

12/1993

Volume

68

Pages

1088 - 1096

Keywords

Animals, Breast Neoplasms, Cloning, Molecular, Culture Media, Conditioned, DNA, Complementary, DNA, Neoplasm, DNA, Recombinant, Drug Resistance, Estradiol, Estrogen Antagonists, Estrogens, Female, Growth Substances, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Transplantation, Polyunsaturated Alkamides, Receptors, Estrogen, Tamoxifen, Transfection, Tumor Cells, Cultured, Tumor Stem Cell Assay