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Expression of transforming growth factor α antisense mRNA inhibits the estrogen‐induced production of TGFα and estrogen‐induced proliferation of estrogen‐responsive human breast cancer cells
Author(s) -
Kenney N. J.,
Saeki T.,
Gottardis M.,
Kim N.,
GarciaMorales P.,
Martin M. B.,
Normanno N.,
Ciardiello F.,
Day A.,
Cutler M. L.,
Salomon D. S.
Publication year - 1993
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041560309
Subject(s) - estrogen , transforming growth factor , biology , microbiology and biotechnology , estrogen receptor , cell culture , endogeny , estrogen receptor alpha , messenger rna , cell growth , endocrinology , growth factor , tgf alpha , medicine , gene , receptor , cancer , breast cancer , biochemistry , genetics
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) Apa 1‐ Eco 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 μM CdCl 2 , 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 CdCl 2 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 CdCl 2 . 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 CdCl 2 , whereas the ADG and AIG of MH‐1 mass‐infected HS‐578T cells, a TGFα‐negative cell line, were unaffected by CdCl 2 treatment. These results suggest that TGFα may be one important autocrine intermediary in regulating estrogen‐induced cell proliferation. © 1993 Wiley‐Liss, Inc.