IIp45, an insulin-like growth factor binding protein 2 (IGFBP-2) binding protein, antagonizes IGFBP-2 stimulation of glioma cell invasion.
Our previous studies have shown that insulin-like growth factor binding protein 2 (IGFBP-2) is frequently overexpressed in the highly invasive glioblastoma multiforme (GBM). By using a yeast two-hybrid system, we identified a gene, invasion inhibitory protein 45 (IIp45), whose protein product bound to IGFBP-2 through the thyroglobulin-RGD region of the C terminus of IGFBP-2. The IIp45 gene is located on chromosome 1p36 and has nine exons. The IIp45 protein has three SEG (segment of low compositional complexity) domains and an integrin-binding RGD motif. The IIp45 protein was not expressed in some GBMs. Functional studies showed that IIp45 inhibited GBM cell invasion both in vitro and in xenograft model. Gene expression profiling studies showed that IIp45 consistently inhibited the expression of cell invasion-associated genes, such as the transcriptional NFkappaB, and its downstream target gene, intercellular adhesion molecule 1. Thus, we report here the isolation and characterization of a gene, IIp45, whose protein product binds to IGFBP-2 and inhibits glioma cell invasion.
Song
Sonya W
SW
Department of Pathology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Fuller
Gregory N
GN
Khan
Asadullah
A
Kong
Shouming
S
Shen
Weiping
W
Taylor
Ellen
E
Ramdas
Latha
L
Lang
Frederick F
FF
Zhang
Wei
W
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics; D009361:Neoplasm Invasiveness; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D047908:Intracellular Signaling Peptides and Proteins; C480900:MIIP protein, human; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1