Over-expression of the epidermal growth factor receptor in human breast cancer cells fails to induce an estrogen-independent phenotype.
An association exists in primary human breast tumors between high epidermal growth factor receptor (EGFR) expression and a reduced number or even absence of estrogen receptors (ER). To determine whether an increase in EGFR expression might alter the estrogen responsiveness of an ER-positive human breast cancer cell line, ZR 75-1 cells were cotransfected with a plasmid containing the full-length cDNA for the human EGFR under the transcriptional control of the Harvey murine sarcoma virus (HaMSV) long terminal repeat (LTR) and with a pSV2neo plasmid. Two of the isolated G418-resistant clones were found to constitutively express EGFR levels 15- to 60-fold higher than those found on nontransfected ZR 75-1 cells. The EGFR in these clones were functionally normal since EGF could increase their autophosphorylation and since EGF could enhance the transphosphorylation of p185erbB-2. No change was seen in either the number or affinity of ER in these clones. In addition, the ability of estrogen to stimulate the anchorage-dependent and anchorage-independent growth of these clones was not significantly modified. These results suggest that an increase in EGFR expression alone is not sufficient to induce a hormone-independent phenotype in vitro in human breast cancer cells.
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
E M
EM
Valverius
T
T
Velu
V
V
Shankar
F
F
Ciardiello
N
N
Kim
D S
DS
Salomon
D015152:Blotting, Northern; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000032:analysis; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000096:biosynthesis*; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D015870:Gene Expression; D006251:Harvey murine sarcoma virus / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D009376:Neoplasms, Hormone-Dependent; D012313:RNA / Q000032:analysis; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D014162:Transfection
D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D012313:RNA; D004247:DNA; D066246:ErbB Receptors