Abstract:
:We recently found evidence indicating that the source of elevated serum insulin-like growth factor binding protein (IGFBP)-2 in leukemia was the leukemic T-cells. Here we report that locally produced IGF-II affects IGFBP-2 expression and growth of leukemic cells through the IGF type I receptor. We measured IGFBP-2, -4 and IGF type I receptor (IGF-I-R) mRNA by RT-PCR, cell growth and IGFBP-2 secretion (per 10(6) cells). IGF-I-R binding sites were assessed by 125I-IGF replacement studies. Inhibition using an IGF-II antibody showed that tumor cell-derived IGF-II accounts for a significant 25% (P < 0.001) increase in IGFBP-2 secretion and enhanced growth (P < 0.01) of leukemic T-cells after 7 days in culture. IGFBP-2 secretion, but not IGFBP-2 mRNA was specifically increased by IGFs, while no specific effect of insulin was detectable. The addition of 100 ng/ml IGF-II enhanced the IGFBP-2 secretion 2.8-fold, while the use of IGF-I only enhanced IGFBP-2 secretion 1.7-fold, although IGF-I enhanced IGF-II action. Through inhibition using JB1, a peptide inhibiting the IGF signal transduction by blocking the IGF-I-R, we demonstrated the involvement of the IGF-I-R in IGFBP-2 and -4 expression and leukemic cell growth. However, only slight differences in the IGF-I-R mRNA expression were seen for T- and B-cells compared with the differences found for the IGFBP-2 and -4 mRNA or IGFBP-2 secretion. Thus, although IGF-I-R mediates the autocrine/paracrine effects of the IGFs, IGF-I-R mRNA expression is most probably not involved in the differential IGFBP-2/IGFBP-4 expression in leukemic cells.
journal_name
Eur J Endocrinoljournal_title
European journal of endocrinologyauthors
Elmlinger MW,Sanatani MS,Bell M,Dannecker GE,Ranke MBdoi
10.1530/eje.0.1380337subject
Has Abstractpub_date
1998-03-01 00:00:00pages
337-43issue
3eissn
0804-4643issn
1479-683Xjournal_volume
138pub_type
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-08-0688
更新日期:2009-04-01 00:00:00
abstract:OBJECTIVE:IGF1 is essential for human growth and mediates its effects through the type 1 IGF receptor (IGF1R). Our objective was to determine the frequency of certain previously reported IGF1R gene variants in the normal population and their effect on stature. DESIGN:A cross-sectional study was conducted in a populati...
journal_title:European journal of endocrinology
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journal_title:European journal of endocrinology
pub_type: 杂志文章,随机对照试验
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更新日期:2011-08-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-16-0956
更新日期:2017-04-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
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更新日期:2018-02-01 00:00:00
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journal_title:European journal of endocrinology
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doi:10.1530/eje.0.1450497
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-12-1035
更新日期:2013-05-10 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,随机对照试验
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更新日期:2016-06-01 00:00:00
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更新日期:2020-12-01 00:00:00
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journal_title:European journal of endocrinology
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更新日期:2001-03-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/EJE-07-0355
更新日期:2007-12-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:2010-10-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:2008-02-01 00:00:00
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journal_title:European journal of endocrinology
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doi:10.1530/eje.0.1510735
更新日期:2004-12-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-09-0044
更新日期:2009-07-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:2016-11-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
doi:10.1530/eje.0.1330235
更新日期:1995-08-01 00:00:00
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更新日期:2015-08-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2015-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2009-09-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:2010-07-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:2007-10-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:1997-12-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1994-08-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:2012-07-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
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更新日期:2019-07-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章
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更新日期:2017-04-01 00:00:00
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journal_title:European journal of endocrinology
pub_type: 杂志文章,评审
doi:10.1530/EJE-08-0314
更新日期:2008-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1530/eje.0.1430047
更新日期:2000-07-01 00:00:00