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Thyroid hormone is a MAPK dependent growth factor for human myeloma cells acting via {alpha}v{beta}3 integrin.
MedLine Citation:
PMID:  21821675     Owner:  NLM     Status:  Publisher    
Experimental and clinical observations suggest that thyroid hormone (L-thyroxine, T4, and 3, 5, 3'-triiodo-L-thyronine, T3) can support cancer cell proliferation. T3 and T4 promote both tumor cell division and angiogenesis by activating mitogen-activated protein kinase (MAPK) via binding to a hormone receptor on the αvβ3 integrin, over-expressed on many cancer cells. We have studied the responsiveness of several MM cell lines to T3 and T4 and characterized hormonal effects on cell survival, proliferation and MAPK activation. Overnight T3 (1-100 nM) and T4 (100 nM) incubation enhanced, up to 50% (p <0.002), MM cell viability (WST-1 assay) and increased cell proliferation by 30%-60% (p <0.01). Short exposure (10-minutes) to T3 and T4 increased MAPK activity by 2.5-3.5-fold (p <0.03). Pharmacological MAPK Inhibition blocked the proliferative action of T3 and T4. Antibodies to the integrin αvβ3 dimer and to αv and β3 monomers (but not β1) inhibited MAPK activation and subsequent cell proliferation in response to thyroid hormone, indicating dependence upon this integrin. Moreover, tetraiodothyroacetic acid (tetrac), a non-agonist T4 analog previously shown to selectively block T3/T4 binding to αvβ3 receptor site, blocked induction of MAPK by the hormones in a dose-dependent manner. This demonstration of the role of thyroid hormones as growth factors for MM cells may offer novel therapeutic approaches.
Keren Cohen; Martin Ellis; Shafik Khoury; Paul J Davis; Aleck Hercbergs; Osnat Ashur-Fabian
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-5
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  -     ISSN:  1557-3125     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Meir Medical Center.
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