Transfection of human estrogen receptor (ER) cDNA into ER-negative mammalian cell lines.
Estrogen responsiveness of breast tumors can be correlated with the presence or absence of the estrogen receptor (ER). Breast cancer cells that contain ER are, in general, responsive to stimulation by estrogen both in vivo and in vitro; therefore hormonal control is possible. Breast tumors that lose the ER, and become hormone-independent are refractory to the direct effect of estrogens and antiestrogens. It is therefore of interest to determine whether the re-expression of the ER will be sufficient to make ER-negative cells sensitive to the growth effect of estrogen. Transfection experiments with wild type and mutant ER cDNAs into different mammalian cell lines have been performed to re-establish hormonal control over hormone-independent cells. Paradoxically, introduction of exogenous ER into ER-negative cells and treatment with estrogen leads to growth inhibition rather than growth promotion. The activation of a number of estrogen-regulated genes has been examined in ER-transfectants but gene regulation is often variable. It is clear that the transfection of the ER gene into cells lacking this protein does not simply re-create the native ER-positive phenotype. Studies need to be extended to identify either the transcription factors that interact with ER to cause the negative effects of estrogen indirectly ("squelching") or the precise target genes that cause growth inhibition directly.
Levenson
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AS
Robert H. Lurie Cancer Center, Northwestern University Medical School, Chicago, IL 60611.
Jordan
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VC
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D018076:DNA, Complementary; D004967:Estrogens / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011960:Receptors, Estrogen / Q000235:genetics* / Q000502:physiology; D014162:Transfection
D018076:DNA, Complementary; D004967:Estrogens; D011960:Receptors, Estrogen