IGF-I and IGFBP-3 augment transforming growth factor-beta actions in human renal carcinoma cells.
(2006) In Kidney International 70(9). p.1584-1590- Abstract
- Renal cell carcinoma (RCC) is the most prevalent cancer of the kidney. In human RCC cells, we recently showed that insulin-like growth factor I (IGF-I) has growth-promoting effects regulated by IGF-binding protein 3 (IGFBP-3). In this study, the analysis was expanded to include the interaction between the IGF and transforming growth factor-beta (TGF-beta) systems in the human RCC cells Caki-2 (from a primary tumor) and SK-RC-52 (from a metastasis). Functional effects such as cell proliferation, TGF-beta receptor (T beta R) signaling, and IGFBP-3 levels were monitored after stimulation with various concentrations of IGF-I, TGF-beta, and IGFBP-3. In addition, human RCC tissues as well as experimental human RCC tumors were analyzed for... (More)
- Renal cell carcinoma (RCC) is the most prevalent cancer of the kidney. In human RCC cells, we recently showed that insulin-like growth factor I (IGF-I) has growth-promoting effects regulated by IGF-binding protein 3 (IGFBP-3). In this study, the analysis was expanded to include the interaction between the IGF and transforming growth factor-beta (TGF-beta) systems in the human RCC cells Caki-2 (from a primary tumor) and SK-RC-52 (from a metastasis). Functional effects such as cell proliferation, TGF-beta receptor (T beta R) signaling, and IGFBP-3 levels were monitored after stimulation with various concentrations of IGF-I, TGF-beta, and IGFBP-3. In addition, human RCC tissues as well as experimental human RCC tumors were analyzed for cellular expression of phosphorylated Smad2 by immunohistochemistry. TGF-beta regulated the endogenous IGFBP-3 levels in these RCC cells as neutralizing anti-TGF-beta(1-3) antibodies strongly reduced the basal IGFBP-3 level. In addition, IGF-I increased the IGFBP-3 levels five- to eightfold with TGF-beta acting in synergy to enhance the IGFBP-3 levels 12- to 17-fold. Neutralizing TGF-beta(1-3) activity circumvented the growth inhibitory effects of IGFBP-3 seen in SK-RC-52, whereas it inhibited the growth-promoting effects of IGFBP-3 in Caki-2. Moreover, IGF-I interacted directly with TGF-beta activation of the TbR complex by enhancing phosphorylation and nuclear translocation of Smad2. This study demonstrates a direct interaction of the IGF and TGF-beta systems in human renal carcinoma cells. The observations that IGF-I enhances the TGF-beta signaling and that TGF-beta promotes IGFBP-3 production and thus influence the biological activity of IGF may be of importance for future therapeutic options. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/161030
- author
- Rosendahl, Ann LU and Forsberg, G
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- renal, cell carcinoma, IGFBP-3, IGF, TGF-beta, neutralization, Smad2 phosphorylation
- in
- Kidney International
- volume
- 70
- issue
- 9
- pages
- 1584 - 1590
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:16969385
- wos:000241667200016
- scopus:33750209892
- pmid:16969385
- ISSN
- 1523-1755
- DOI
- 10.1038/sj.ki.5001805
- language
- English
- LU publication?
- yes
- id
- d8f551b2-3367-48cd-bbcf-dcaca043ae05 (old id 161030)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16969385&dopt=Abstract
- date added to LUP
- 2016-04-01 16:33:26
- date last changed
- 2022-03-30 08:41:23
@article{d8f551b2-3367-48cd-bbcf-dcaca043ae05,
abstract = {{Renal cell carcinoma (RCC) is the most prevalent cancer of the kidney. In human RCC cells, we recently showed that insulin-like growth factor I (IGF-I) has growth-promoting effects regulated by IGF-binding protein 3 (IGFBP-3). In this study, the analysis was expanded to include the interaction between the IGF and transforming growth factor-beta (TGF-beta) systems in the human RCC cells Caki-2 (from a primary tumor) and SK-RC-52 (from a metastasis). Functional effects such as cell proliferation, TGF-beta receptor (T beta R) signaling, and IGFBP-3 levels were monitored after stimulation with various concentrations of IGF-I, TGF-beta, and IGFBP-3. In addition, human RCC tissues as well as experimental human RCC tumors were analyzed for cellular expression of phosphorylated Smad2 by immunohistochemistry. TGF-beta regulated the endogenous IGFBP-3 levels in these RCC cells as neutralizing anti-TGF-beta(1-3) antibodies strongly reduced the basal IGFBP-3 level. In addition, IGF-I increased the IGFBP-3 levels five- to eightfold with TGF-beta acting in synergy to enhance the IGFBP-3 levels 12- to 17-fold. Neutralizing TGF-beta(1-3) activity circumvented the growth inhibitory effects of IGFBP-3 seen in SK-RC-52, whereas it inhibited the growth-promoting effects of IGFBP-3 in Caki-2. Moreover, IGF-I interacted directly with TGF-beta activation of the TbR complex by enhancing phosphorylation and nuclear translocation of Smad2. This study demonstrates a direct interaction of the IGF and TGF-beta systems in human renal carcinoma cells. The observations that IGF-I enhances the TGF-beta signaling and that TGF-beta promotes IGFBP-3 production and thus influence the biological activity of IGF may be of importance for future therapeutic options.}},
author = {{Rosendahl, Ann and Forsberg, G}},
issn = {{1523-1755}},
keywords = {{renal; cell carcinoma; IGFBP-3; IGF; TGF-beta; neutralization; Smad2 phosphorylation}},
language = {{eng}},
number = {{9}},
pages = {{1584--1590}},
publisher = {{Nature Publishing Group}},
series = {{Kidney International}},
title = {{IGF-I and IGFBP-3 augment transforming growth factor-beta actions in human renal carcinoma cells.}},
url = {{http://dx.doi.org/10.1038/sj.ki.5001805}},
doi = {{10.1038/sj.ki.5001805}},
volume = {{70}},
year = {{2006}},
}