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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-4-5
pubmed:abstractText
The activation of the insulin-like growth factor 1/IGF1 receptor system (IGF1/IGF1R) is a critical event in the transformation and tumorigenicity processes in a wide variety of human tumors. The IGF1/IGF1R system has been recently studied in carcinoid tumors that often arise in the gastrointestinal tract; these tumors are characterized by hypersecretion of bioamines and neuropeptides, leading to functional tumor disease. Two alternatively spliced IGF1R mRNA transcripts have been described to differ by only three nucleotides (CAG) in the coding sequence, resulting in an amino-acid change from the originally described Thr-Gly to an Arg in the extracellular portion of the receptor beta subunit. In transfected Chinese hamster ovary cells, the form without CAG (CAG-) exhibited an approximate 2-fold increase in IGF1 stimulation of activities required for its mitogenic properties. In this study, we examine the relative expression of the two IGF1R mRNA isoforms by a semiquantitative RT-PCR approach using highly standardized conditions, beta-2 microglobulin (B2M) as a reference gene and gel imaging analysis. We analyzed a large series of human neuroendocrine tumors (32 samples) and 9 normal tissues. A significant higher expression of both isoforms in the tumor samples (approximately 2-fold increase) was found, while a constant CAG+/CAG- IGF1R mRNA isoforms of an approximate 3:1 ratio was observed in all tumoral and normal cell types studied. The phylogenetic study of the IGF1R locus in several species suggests that human IGF1R CAG- mRNA isoform is evolutionarily more recent compared to the IGF1R CAG+ mRNA isoform and it could be used by the splicing apparatus at this intron/exon junction with a lower efficiency. This study highlights the relevance of IGF1R mRNA expression in neuroendocrine tumor cells, and the constant presence of 'subtle' alternative splicing for the IGF1R locus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1021-335X
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1249-56
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16596194-Adult, pubmed-meshheading:16596194-Aged, pubmed-meshheading:16596194-Alternative Splicing, pubmed-meshheading:16596194-Amino Acid Sequence, pubmed-meshheading:16596194-Carcinoma, Islet Cell, pubmed-meshheading:16596194-Cell Differentiation, pubmed-meshheading:16596194-DNA Primers, pubmed-meshheading:16596194-Female, pubmed-meshheading:16596194-Head and Neck Neoplasms, pubmed-meshheading:16596194-Humans, pubmed-meshheading:16596194-Male, pubmed-meshheading:16596194-Middle Aged, pubmed-meshheading:16596194-Molecular Sequence Data, pubmed-meshheading:16596194-Neuroendocrine Tumors, pubmed-meshheading:16596194-Protein Isoforms, pubmed-meshheading:16596194-RNA, Messenger, pubmed-meshheading:16596194-RNA, Neoplasm, pubmed-meshheading:16596194-Receptor, IGF Type 1, pubmed-meshheading:16596194-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:16596194-Sequence Homology, Amino Acid
pubmed:year
2006
pubmed:articleTitle
Differential expression of alternatively spliced mRNA forms of the insulin-like growth factor 1 receptor in human neuroendocrine tumors.
pubmed:affiliation
Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, I-40126 Bologna, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't