Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1995-5-3
pubmed:abstractText
Breast cancer cell lines have been shown to secrete transforming growth factor alpha (TGF alpha) and other polypeptide growth factors in response to estrogen (E2) stimulation. In this study, we investigated whether cellular-derived TGF alpha mediates the growth-stimulatory effects of E2 in ER-positive breast cancer cells. To test this hypothesis, we introduced an antisense TGF alpha mRNA expression vector under control of a human metallothionein promoter into E2-responsive T47D human breast cancer cells. In stably transfected cells, cadmium induced antisense mRNA and reduced expression of TGF alpha mRNA and protein in antisense clones (AS1). TGF alpha expression was increased in sense clones (S2), while wild-type T47D cells (W3) or pSV2 neomycin resistance-transfected cells showed no change in TGF alpha expression in response to cadmium. The basal proliferative capacity of antisense transfected cells was equivalent to that of the wild-type. E2 increased TGF alpha synthesis and cell proliferation in transfected and wild-type cells. In AS1 cells, the simultaneous addition of cadmium with E2 blocked most of the E2-induced increase in TGF alpha mRNA and protein and nearly abolished the stimulatory effects of E2 on DNA synthesis and cell number. In contrast, no reduction in cell proliferation was observed with cadmium in antisense-transfected cells with a low level of antisense expression or in the S2 or W3 cells. Our results are compatible with the hypothesis that autocrine production of TGF alpha may be an important contributor to E2-induced growth in T47D cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1044-9523
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1275-82
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Inhibition of estrogen-induced breast cancer cell proliferation by reduction in autocrine transforming growth factor alpha expression.
pubmed:affiliation
Department of Medicine/Medicaal Oncology, University of Texas Health Science Center at San Antonio 78284-7884.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.