Emergence of MCF-7 cells overexpressing a transfected epidermal growth factor receptor (EGFR) under estrogen-depleted conditions: Evidence for a role of EGFR in breast cancer growth and progression

D. L. Miller, D. El-Ashry, Andrea L Cheville, Y. Liu, S. W. McLeskey, F. G. Kern

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Abstract

Overexpression of epidermal growth factor receptor (EGFR) is correlated with loss of estrogen receptor and poor prognosis in breast cancer. To investigate this phenomenon, we transfected a cytomegalovirus expression vector directing the expression of EGFR into estrogen receptor-positive MCF- 7 breast cancer cells and into a clone of MCF-7 cells previously transfected with transforming growth factor α. Cells arising from single clones or pooled polyclonal population maintained in charcoal-stripped calf serum, a medium devoid of estrogen, overexpressed EGFR. Switching these cells to a medium containing fetal calf serum or charcoal-stripped calf serum plus 17β- estradiol resulted in the emergence of a population expressing low EGFR levels. Loss of expression was not a consequence of nonspecific repression of the cytomegalovirus promoter, because expression of the fibroblast growth factor (FGF)-4 complementary DNA in a similar vector was not lost in fetal calf serum. While loss of EGFR overexpression in fetal calf serum was seen at both the protein and mRNA levels, Southern blotting shows that this was not due to loss of the transfected gene. Subclones of a cell population with low EGFR expression were capable of increasing expression upon estrogen withdrawal, demonstrating that the changes in EGFR expression were reversible and suggesting a growth advantage conferred by EGFR overexpression under these restrictive growth conditions. Overexpression of EGFR did not result in loss of ER expression. These results suggest a role for overexpression of EGFR in the growth of estrogen receptor-positive breast cancer cells in the absence of estrogen.

Original languageEnglish (US)
Pages (from-to)1263-1274
Number of pages12
JournalCell Growth and Differentiation
Volume5
Issue number12
StatePublished - 1994
Externally publishedYes

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MCF-7 Cells
Epidermal Growth Factor Receptor
Estrogens
Breast Neoplasms
Growth
Estrogen Receptors
Serum
Charcoal
Cytomegalovirus
Fibroblast Growth Factor 4
Clone Cells
Population
Transforming Growth Factors
Southern Blotting
Estradiol
Complementary DNA
Messenger RNA

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

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abstract = "Overexpression of epidermal growth factor receptor (EGFR) is correlated with loss of estrogen receptor and poor prognosis in breast cancer. To investigate this phenomenon, we transfected a cytomegalovirus expression vector directing the expression of EGFR into estrogen receptor-positive MCF- 7 breast cancer cells and into a clone of MCF-7 cells previously transfected with transforming growth factor α. Cells arising from single clones or pooled polyclonal population maintained in charcoal-stripped calf serum, a medium devoid of estrogen, overexpressed EGFR. Switching these cells to a medium containing fetal calf serum or charcoal-stripped calf serum plus 17β- estradiol resulted in the emergence of a population expressing low EGFR levels. Loss of expression was not a consequence of nonspecific repression of the cytomegalovirus promoter, because expression of the fibroblast growth factor (FGF)-4 complementary DNA in a similar vector was not lost in fetal calf serum. While loss of EGFR overexpression in fetal calf serum was seen at both the protein and mRNA levels, Southern blotting shows that this was not due to loss of the transfected gene. Subclones of a cell population with low EGFR expression were capable of increasing expression upon estrogen withdrawal, demonstrating that the changes in EGFR expression were reversible and suggesting a growth advantage conferred by EGFR overexpression under these restrictive growth conditions. Overexpression of EGFR did not result in loss of ER expression. These results suggest a role for overexpression of EGFR in the growth of estrogen receptor-positive breast cancer cells in the absence of estrogen.",
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T2 - Evidence for a role of EGFR in breast cancer growth and progression

AU - Miller, D. L.

AU - El-Ashry, D.

AU - Cheville, Andrea L

AU - Liu, Y.

AU - McLeskey, S. W.

AU - Kern, F. G.

PY - 1994

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