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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0021665,
umls-concept:C0037083,
umls-concept:C0086597,
umls-concept:C0185117,
umls-concept:C0532623,
umls-concept:C0596290,
umls-concept:C1149301,
umls-concept:C1334882,
umls-concept:C1515877,
umls-concept:C1705029,
umls-concept:C1710082,
umls-concept:C1879547,
umls-concept:C2911684
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pubmed:issue |
6
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pubmed:dateCreated |
2009-3-18
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pubmed:abstractText |
NKX3.1 is a homeobox gene that codes for a haploinsufficient prostate cancer tumor suppressor. NKX3.1 protein levels are down-regulated in the majority of primary prostate cancer tissues. NKX3.1 expression in PC-3 cells increased insulin-like growth factor binding protein-3 (IGFBP-3) mRNA expression 10-fold as determined by expression microarray analysis. In both stably and transiently transfected PC-3 cells and in LNCaP cells, NKX3.1 expression increased IGFBP-3 mRNA and protein expression. In prostates of Nkx3.1 gene-targeted mice Igfbp-3 mRNA levels correlated with Nkx3.1 copy number. NKX3.1 expression in PC-3 cells attenuated the ability of insulin-like growth factor-I (IGF-I) to induce phosphorylation of type I IGF receptor (IGF-IR), insulin receptor substrate 1, phosphatidylinositol 3-kinase, and AKT. The effect of NKX3.1 on IGF-I signaling was not seen when cells were exposed to long-R3-IGF-I, an IGF-I variant peptide that does not bind to IGFBP-3. Additionally, small interfering RNA-induced knockdown of IGFBP-3 expression partially reversed the attenuation of IGF-IR signaling by NKX3.1 and abrogated NKX3.1 suppression of PC-3 cell proliferation. Thus, there is a close relationship in vitro and in vivo between NKX3.1 and IGFBP-3. The growth-suppressive effects of NKX3.1 in prostate cells are mediated, in part, by activation of IGFBP-3 expression.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/IGFBP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/NKX3-1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1538-7445
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
69
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2615-22
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19258508-Animals,
pubmed-meshheading:19258508-Cell Growth Processes,
pubmed-meshheading:19258508-Cell Line, Tumor,
pubmed-meshheading:19258508-Gene Expression,
pubmed-meshheading:19258508-Glioblastoma,
pubmed-meshheading:19258508-Homeodomain Proteins,
pubmed-meshheading:19258508-Humans,
pubmed-meshheading:19258508-Insulin-Like Growth Factor Binding Protein 3,
pubmed-meshheading:19258508-Insulin-Like Growth Factor Binding Proteins,
pubmed-meshheading:19258508-Insulin-Like Growth Factor I,
pubmed-meshheading:19258508-Male,
pubmed-meshheading:19258508-Mice,
pubmed-meshheading:19258508-Prostatic Neoplasms,
pubmed-meshheading:19258508-RNA, Messenger,
pubmed-meshheading:19258508-Signal Transduction,
pubmed-meshheading:19258508-Transcription Factors,
pubmed-meshheading:19258508-Transfection,
pubmed-meshheading:19258508-Transplantation, Heterologous
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pubmed:year |
2009
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pubmed:articleTitle |
NKX3.1 activates expression of insulin-like growth factor binding protein-3 to mediate insulin-like growth factor-I signaling and cell proliferation.
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pubmed:affiliation |
Lombardi Comprehensive Cancer Center, Washington, District of Columbia, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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