Expression of transforming growth factor α antisense mRNA inhibits the estrogen-induced production of TGFa and estrogen-induced proliferation of estrogen-responsive human breast cancer cells

N. J. Kenney, T. Saeki, M. Gottardis, N. Kim, P. Garcia-Morales, M. B. Martin, N. Normanno, F. Ciardiello, A. Day, M. L. Cutler, D. S. Salomon

Research output: Contribution to journalArticle

Abstract

To ascertain if 17β-estradiol (E2)-induced proliferation could be attenuated by blocking the expression of endogenous transforming growth factor α (TGFα), estrogen receptor (ER)-positive, estrogen-responsive MCF-7 or ZR-75-1 cells and ER-negative, estrogen-nonresponsive MDA-MB-468 or HS-578T cells were infected with a recombinant amphotropic, replication-defective retroviral expression vector containing a 435 base pair (bp) Apal-fco R1 coding fragment of the human TGFα cDNA oriented in the 3′ to 5′ direction and under the transcriptional control of an internal heavy metal-inducible mouse metallothionein (MT-1) promoter and containing the neomycin (neo) resistance gene. E2-stimulated expression of endogenous TGFα mRNA was inhibited by 4-5-fold, and the production of TGFα protein was inhibited by 50-80% when M-1 mass-infected MCF-7 or MZ-1 mass-infected ZR-75-1 cells were treated with 0.75-1 μCdCl2, whereas in comparably treated parental MCF-7 or ZR-75-1 cells there was no significant effect upon these parameters. E2-stimulated anchorage-dependent growth (ADG) and anchorage-independent growth (AIG) of the M-1 or MZ-1 cells was inhibited by 60-90% following CdCl2 treatment. In contrast, neither the ADG nor AIG of the parental noninfected MCF-7 or ZR-75-1 cells that were maintained in the absence or presence of E2 was affected by comparable concentrations of CdCl2 The ADG and AIG of TGFα antisense MD-1 mass-infected MDA-MB-468 cells that express high levels of endogenous TGFα mRNA were also inhibited by 1 μM CdCl2, whereas the ADG and AIG of MH-1 mass-infected HS-578T cells, a TGFα-negative cell line, were unaffected by CdCl2 treatment. These results suggest that TGFα may be one important autocrine intermediary in regulating estrogen-induced cell proliferation.

Original languageEnglish
Pages (from-to)497-514
Number of pages18
JournalJournal of Cellular Physiology
Volume156
Issue number3
Publication statusPublished - Sep 1993

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Transforming Growth Factors
Estrogens
Cadmium Chloride
Cells
Breast Neoplasms
Messenger RNA
Growth
Estrogen Receptors
Neomycin
Growth Factor Receptors
Metallothionein
Cell proliferation
Heavy Metals
Base Pairing
Estradiol
Complementary DNA
Genes
Cell Proliferation
Cell Line

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Expression of transforming growth factor α antisense mRNA inhibits the estrogen-induced production of TGFa and estrogen-induced proliferation of estrogen-responsive human breast cancer cells. / Kenney, N. J.; Saeki, T.; Gottardis, M.; Kim, N.; Garcia-Morales, P.; Martin, M. B.; Normanno, N.; Ciardiello, F.; Day, A.; Cutler, M. L.; Salomon, D. S.

In: Journal of Cellular Physiology, Vol. 156, No. 3, 09.1993, p. 497-514.

Research output: Contribution to journalArticle

Kenney, NJ, Saeki, T, Gottardis, M, Kim, N, Garcia-Morales, P, Martin, MB, Normanno, N, Ciardiello, F, Day, A, Cutler, ML & Salomon, DS 1993, 'Expression of transforming growth factor α antisense mRNA inhibits the estrogen-induced production of TGFa and estrogen-induced proliferation of estrogen-responsive human breast cancer cells', Journal of Cellular Physiology, vol. 156, no. 3, pp. 497-514.
Kenney, N. J. ; Saeki, T. ; Gottardis, M. ; Kim, N. ; Garcia-Morales, P. ; Martin, M. B. ; Normanno, N. ; Ciardiello, F. ; Day, A. ; Cutler, M. L. ; Salomon, D. S. / Expression of transforming growth factor α antisense mRNA inhibits the estrogen-induced production of TGFa and estrogen-induced proliferation of estrogen-responsive human breast cancer cells. In: Journal of Cellular Physiology. 1993 ; Vol. 156, No. 3. pp. 497-514.
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abstract = "To ascertain if 17β-estradiol (E2)-induced proliferation could be attenuated by blocking the expression of endogenous transforming growth factor α (TGFα), estrogen receptor (ER)-positive, estrogen-responsive MCF-7 or ZR-75-1 cells and ER-negative, estrogen-nonresponsive MDA-MB-468 or HS-578T cells were infected with a recombinant amphotropic, replication-defective retroviral expression vector containing a 435 base pair (bp) Apal-fco R1 coding fragment of the human TGFα cDNA oriented in the 3′ to 5′ direction and under the transcriptional control of an internal heavy metal-inducible mouse metallothionein (MT-1) promoter and containing the neomycin (neo) resistance gene. E2-stimulated expression of endogenous TGFα mRNA was inhibited by 4-5-fold, and the production of TGFα protein was inhibited by 50-80{\%} when M-1 mass-infected MCF-7 or MZ-1 mass-infected ZR-75-1 cells were treated with 0.75-1 μCdCl2, whereas in comparably treated parental MCF-7 or ZR-75-1 cells there was no significant effect upon these parameters. E2-stimulated anchorage-dependent growth (ADG) and anchorage-independent growth (AIG) of the M-1 or MZ-1 cells was inhibited by 60-90{\%} following CdCl2 treatment. In contrast, neither the ADG nor AIG of the parental noninfected MCF-7 or ZR-75-1 cells that were maintained in the absence or presence of E2 was affected by comparable concentrations of CdCl2 The ADG and AIG of TGFα antisense MD-1 mass-infected MDA-MB-468 cells that express high levels of endogenous TGFα mRNA were also inhibited by 1 μM CdCl2, whereas the ADG and AIG of MH-1 mass-infected HS-578T cells, a TGFα-negative cell line, were unaffected by CdCl2 treatment. These results suggest that TGFα may be one important autocrine intermediary in regulating estrogen-induced cell proliferation.",
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AU - Gottardis, M.

AU - Kim, N.

AU - Garcia-Morales, P.

AU - Martin, M. B.

AU - Normanno, N.

AU - Ciardiello, F.

AU - Day, A.

AU - Cutler, M. L.

AU - Salomon, D. S.

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