mRNA expression of the type I growth factor receptors in the human breast cancer cells MCF-7: regulation by estradiol and tamoxifen.
BACKGROUND
We recently confirmed, in a series of 365 human breast cancers, that EGFR and c-erbB-2 were associated with estradiol receptors (ER) and/or progesterone receptors (PgR)-negative tumors. Conversely, we demonstrated that c-erbB-3 and c-erbB-4 were positively related to ER and PgR. In the present paper, we simultaneously quantified, for the first time, the mRNA expression of these four receptors in response to estradiol and 4-hydroxy-tamoxifen in the prototypical ER-positive human breast cancer cell line MCF-7.


METHODS
The mRNA expression of the type I growth factor receptors was quantified with a one-step real-time RT-PCR assay.


RESULTS
Estradiol down-regulates the mRNA expression of the four receptors. The EGFR decrease is maximal (30% under the control) for 10(-11) M estradiol. For the three other receptors, the decrease (50% under the control) in mRNA expression is maximal with 10(-9) M. These effects are completely abolished by 4-OH tamoxifen at 10(-6) M.


CONCLUSIONS
In MCF-7 cells, we demonstrate that c-erbB-4 is down-regulated by estradiol and up-regulated by 4-OH tamoxifen, and confirm that the three other receptors followed the same pattern of expression.
Revillion
Françoise
F
Laboratoire d'Oncologie Moléculaire Humaine, Centre Oscar Lambret, 3 rue Frédéric Combemale, BP 309, 59020 Lille, France. f-revillion@olambret.fr
Pawlowski
Valérie
V
Lhotellier
Valérie
V
Louchez
Marie-Michèle
MM
Peyrat
Jean-Philippe
JP
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D004967:Estrogens; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018815:Genes, erbB; D018773:Genes, erbB-1; D018734:Genes, erbB-2; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D020893:Receptor, ErbB-3 / Q000096:biosynthesis; D066247:Receptor, ErbB-4; D011960:Receptors, Estrogen / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D018931:Antineoplastic Agents, Hormonal; D066246:ErbB Receptors; D004958:Estradiol; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C016601:afimoxifene; C587689:ERBB4 protein, human