Estradiol-independent growth of a subline of MCF-7 human breast cancer cells in culture.
An estrogen-independent variant (R3) was selected by cloning wild type MCF-7 cells in soft agar in the presence of tamoxifen. R3 has a slightly slower growth rate under optimal growth conditions. Estradiol and tamoxifen have minimal effects on growth rate and thymidine incorporation as compared to wild type MCF-7 cells. R3 contains both cytoplasmic receptor and a receptor derived from crude nuclear extract with slightly higher numbers of cytosol receptor than wild type MCF-7. The same dissociation constant (Kd) and the same molecular weight (estimated by Sephadex chromatography) and sucrose density behavior for both cytoplasmic and nuclear estrogen receptor are seen in R3 and MCF-7. Estrogen receptor complexes were activated by salt and nucleotide and translocated to the nucleus equivalently in R3 and MCF-7. Relative binding affinities and extent of competition by estradiol and tamoxifen for cytoplasmic estrogen receptor are the same for MCF-7 and R3. Induction of progesterone receptor and nuclear estrogen receptor processing following treatment with estradiol in R3 is minimal compared with MCF-7. DNA affinity (as assessed by DNA cellulose chromatography) of estrogen receptor complexes from R3 and MCF-7 is different. R3 appears to represent a cell with a defect expressed in receptor function apart from the initial hormone-binding step.
D001943:Breast Neoplasms / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007700:Kinetics; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004958:Estradiol