Linked Life Data

9659296

Source:http://linkedlifedata.com/resource/pubmed/id/9659296

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-7-30
pubmed:abstractText
IGF-I has been proposed as a key regulator of mammary epithelial cell (MEC) growth and differentiation. As IGF-I bioactivity is modulated by specific, high-affinity binding proteins (IGFBP), the forms of IGFBP that are secreted by the bovine MEC line, MAC-T, were identified. Media conditioned by MAC-T cells contained four forms of IGFBP that were identified, by western blotting with specific antibodies, as IGFBP-2, -3, -4 and -6. The amounts of IGFBP-3 in conditioned media were relatively low under basal conditions when analyzed by ligand blotting with 125I-IGF-II, but were increased dramatically relative to serum-free controls by exposure to IGF-I (100 ng/ml) or IGF-II (100 ng/ml) for 24 h. These increases in IGFBP-3 protein corresponded with dose-dependent increases in IGFBP-3 mRNA, with IGF-II eliciting a smaller response than was elicited by IGF-I at each concentration. Leu-IGF-I, which has reduced affinity for the IGF-I receptor but normal affinity for IGFBPs, failed to increase IGFBP-3 protein and mRNA levels, whereas B-chain IGF-I (normal affinity for the receptor but reduced affinity for IGFBPs) elicited the response, thus implying an IGF-I receptor-mediated event. Time-course studies indicated that IGFBP-3 mRNA was increased fourfold by 3 h of IGF-I treatment, with maximal increases of eightfold above serum-free controls observed between 8 and 13 h of treatment. By 24 h of treatment, IGFBP-3 mRNA levels had declined and were approximately threefold above controls in cells exposed to IGF-I. Amounts of messenger RNA of IGFBP-6 and IGFBP-2 were not increased by IGF treatment. However, retinoic acid (10(-6) M) stimulated both IGFBP-2 and IGFBP-6 protein and mRNA levels, but it decreased IGFBP-3 mRNA levels relative to controls. The combination of retinoic acid plus IGF-I had no additional effect on IGFBP-6 or -2 above that observed with retinoic acid alone, whereas IGF-I together with retinoic acid attenuated the decrease in IGFBP-3 observed with retinoic acid alone. Protein kinase A-mediated pathways were also shown to alter IGFBP synthesis. Forskolin, which increases cAMP, increased IGFBP-3 protein and mRNA levels. The combination of IGF-I plus forskolin resulted in greater increases in both protein and mRNA than were observed with either treatment alone. In contrast, forskolin decreased IGFBP-6 mRNA relative to controls, but had no effect on IGFBP-2. The decrease in IGFBP-6 was less marked when cells were treated with a combination of IGF-I and forskolin. Forskolin had no effect on IGFBP-2 mRNA levels. In summary, the ability of IGF-I specifically to regulate IGFBP-3 synthesis represents a mechanism whereby IGF-I may regulate its own bioactivity. In addition, the differential regulation of IGFBP-2, -3 and -6 by retinoic acid (which inhibits proliferation) and IGF-I (which stimulates proliferation) suggests that these forms of IGFBP have different roles in regulating mammary epithelial cell physiology.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-0795
pubmed:author
pubmed:issnType
Print
pubmed:volume
157
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
327-36
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9659296-Animals, pubmed-meshheading:9659296-Blotting, Northern, pubmed-meshheading:9659296-Blotting, Western, pubmed-meshheading:9659296-Cattle, pubmed-meshheading:9659296-Cell Line, pubmed-meshheading:9659296-Cyclic AMP, pubmed-meshheading:9659296-Epithelium, pubmed-meshheading:9659296-Female, pubmed-meshheading:9659296-Forskolin, pubmed-meshheading:9659296-Insulin-Like Growth Factor Binding Protein 2, pubmed-meshheading:9659296-Insulin-Like Growth Factor Binding Protein 3, pubmed-meshheading:9659296-Insulin-Like Growth Factor Binding Protein 4, pubmed-meshheading:9659296-Insulin-Like Growth Factor Binding Protein 6, pubmed-meshheading:9659296-Insulin-Like Growth Factor Binding Proteins, pubmed-meshheading:9659296-Insulin-Like Growth Factor I, pubmed-meshheading:9659296-Mammary Glands, Animal, pubmed-meshheading:9659296-Polymerase Chain Reaction, pubmed-meshheading:9659296-RNA, Messenger, pubmed-meshheading:9659296-Tretinoin
pubmed:year
1998
pubmed:articleTitle
Regulation of IGF binding protein synthesis by a bovine mammary epithelial cell line.
pubmed:affiliation
Department of Animal Sciences, Rutgers University, New Brunswick, New Jersey, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't