Linked Life Data

9751635

Source:http://linkedlifedata.com/resource/pubmed/id/9751635

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1998-10-1
pubmed:abstractText
Interleukin-4 (IL-4) is a pleiotropic cytokine produced by mast cells and T lymphocytes that promotes proliferation and immunoglobulin class-switching in B cells. IL-4 receptors (IL-4Rs) are also expressed by nonhematopoietic cells as well as some tumor cells. Unlike its mitogenic effect on B cells, IL-4 inhibits the growth of some cancer cells in vitro. In this study, we show that IL-4R is expressed by breast and ovarian cancer cell lines. Furthermore, anchorage-dependent and -independent growth of breast cancer cell lines MCF-7 and MDA-MB-231 is inhibited by IL-4 treatment, and this effect requires IL-4R. Interestingly, IL-4 only inhibited proliferating breast cancer cells and had no effect on basal, unstimulated growth. We therefore characterized the effect of IL-4 on breast cancer cell growth stimulated by either estradiol or insulin-like growth factor I (IGF-I). In both anchorage-dependent and -independent growth assays, IL-4 inhibited estradiol-stimulated growth. The antiestrogen effect of IL-4 was not due to IL-4 interference with the estrogen receptor, because IL-4 did not interfere with estrogen receptor-mediated reporter gene transactivation. In contrast, IL-4 had no effect on IGF-I-stimulated proliferation. Because IGF-I is known to inhibit programmed cell death, we examined apoptosis as a possible mechanism of IL-4 action. We established that IL-4 induced apoptosis in breast cancer cells by five independent criteria: (a) morphological indicators including pyknotic nuclei and cytoplasmic condensation; (b) DNA fragmentation; (c) the formation of DNA laddering; (d) the cleavage of poly(ADP-ribose) polymerase; and (e) the presence of cells with sub-G1 DNA content. IL-4 increased the percentage of apoptotic cells in MCF-7 and MDA-MB-231 cells 6.0- and 6.7-fold over that of the control, respectively. Finally, the addition of IGF-I reversed IL-4-induced apoptosis, suggesting that the mechanism of IL-4-induced growth inhibition in human breast cancer cells is the induction of programmed cell death.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4199-205
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Interleukin 4 inhibits growth and induces apoptosis in human breast cancer cells.
pubmed:affiliation
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.