PMID- 3221874
OWN - NLM
STAT- MEDLINE
DCOM- 19890323
LR  - 20181130
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 2
IP  - 11
DP  - 1988 Nov
TI  - Blockade of the epidermal growth factor receptor inhibits transforming growth 
      factor alpha-induced but not estrogen-induced growth of hormone-dependent human 
      breast cancer.
PG  - 1064-9
AB  - Transforming growth factor alpha (TGF alpha), a polypeptide that binds to the 
      epidermal growth factor (EGF) receptor, is expressed and secreted by human breast 
      cancer cells and has been proposed as an autocrine growth factor and as a 
      mediator of the mitogenic effect of estrogen. We investigated the potential 
      importance of secreted TGF alpha in estrogen-responsive MCF-7 human breast cancer 
      cells using monoclonal (528ab and 225ab) and polyclonal antibodies that block the 
      EGF/TGF alpha receptor. Confirming other studies, these MCF-7 cells expressed TGF 
      alpha with mRNA transcripts of 4.8 kilobases identified by Northern analysis, and 
      they secreted TGF alpha activity measured by normal rat kidney colony-forming 
      assay and an EGF RRA of conditioned medium. This activity was increased 3-fold by 
      1 nM 17 beta-estradiol and decreased by 1 microM tamoxifen. 528ab and 225ab bound 
      to EGF receptors in MCF-7 cells with high affinity [dissociation constant (Kd) 
      0.1-0.5 nM] and blocked the binding of EGF/TGF alpha. These antibodies failed to 
      inhibit baseline DNA synthesis or growth of MCF-7 cells although they were potent 
      inhibitors of EGF/TGF alpha-induced growth of these cells. We hypothesized that 
      if secreted TGF alpha mediates estrogen-induced growth, then EGF/TGF alpha 
      receptor blockade should inhibit estrogen stimulation. MCF-7 cells were first 
      treated with tamoxifen to inhibit growth and to reduce TGF alpha expression. 
      Under these conditions, estrogen replenishment induced a marked dose-dependent 
      rescue of TGF alpha secretion, DNA synthesis, and cell proliferation. Exogenous 
      TGF alpha also partially restored growth of tamoxifen-inhibited cells. Although 
      the simultaneous addition of 528ab or 225ab blocked TGF alpha-induced rescue of 
      MCF-7 cells, it had no effect on rescue by estradiol.(ABSTRACT TRUNCATED AT 250 
      WORDS)
FAU - Arteaga, C L
AU  - Arteaga CL
AD  - Department of Medicine, University of Texas Health Science Center, San Antonio 
      78284-7884.
FAU - Coronado, E
AU  - Coronado E
FAU - Osborne, C K
AU  - Osborne CK
LA  - eng
GR  - P01-30195/PHS HHS/United States
GR  - R01-CA 30251/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Estrogens)
RN  - 76057-06-2 (Transforming Growth Factors)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Breast Neoplasms/*physiopathology
MH  - Cell Division/drug effects
MH  - ErbB Receptors/*antagonists & inhibitors/pharmacology
MH  - Estrogens/*pharmacology
MH  - Female
MH  - Humans
MH  - Transforming Growth Factors/*pharmacology
MH  - Tumor Cells, Cultured/*drug effects/physiopathology
EDAT- 1988/11/01 00:00
MHDA- 1988/11/01 00:01
CRDT- 1988/11/01 00:00
PHST- 1988/11/01 00:00 [pubmed]
PHST- 1988/11/01 00:01 [medline]
PHST- 1988/11/01 00:00 [entrez]
AID - 10.1210/mend-2-11-1064 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1988 Nov;2(11):1064-9. doi: 10.1210/mend-2-11-1064.