mRNA expression of the type I growth factor receptors in the human breast cancer cells MCF-7: regulation by estradiol and tamoxifen

Anticancer Res. 2003 Mar-Apr;23(2B):1455-60.

Abstract

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.

Materials and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Dose-Response Relationship, Drug
  • ErbB Receptors / biosynthesis
  • Estradiol / pharmacology*
  • Estrogen Receptor Modulators / pharmacology*
  • Estrogens*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, erbB*
  • Genes, erbB-1*
  • Genes, erbB-2*
  • Humans
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / pathology*
  • Proto-Oncogene Proteins*
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • Receptor, ErbB-2 / biosynthesis
  • Receptor, ErbB-3 / biosynthesis
  • Receptor, ErbB-4
  • Receptors, Estrogen / drug effects
  • Receptors, Progesterone / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacology*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism

Substances

  • Antineoplastic Agents, Hormonal
  • Estrogen Receptor Modulators
  • Estrogens
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • afimoxifene
  • Estradiol
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4