Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1658953 (tumor vasculature)
 2,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insulin-responsive R3230AC mammary tumor possesses type I and type II insulin-like growth factor (IGF) receptors, and membrane preparations display affinity cross-linking of 125I-labeled IGF-I to IGF-binding proteins (IGFBPs). To identify the IGFBPs produced, Northern blotting analysis of poly(A)+ RNA extracts from tumor tissue was performed. Although transcripts of IGFBP-1 were not detected, intense bands were obtained at 1.7 and 6 kilobases (kb) when hybridized with radiolabeled IGFBP-2 and IGFBP-5 cDNA probes, respectively. A 2.6-kb band and a 2.4-kb weaker band were observed after hybridization with IGFBP-3 and IGFBP-4 probes, respectively. When IGFBP-6 cDNA was used, two bands were seen: a higher mol wt band at 6.3 kb and a smaller one at 1.3 kb. Tumors from streptozotocin-induced diabetic rats displayed an increase in the expression of IGFBP-2, and insulin treatment for 3 days normalized the IGFBP-2 mRNA levels. Tumors from diabetic rats displayed no change in IGFBP-3, -4, -5, and -6 mRNA levels from tumors of normoglycemic rats. However, tumors from insulin-treated rats showed significantly higher levels of mRNA for IGFBP-4 and IGFBP-5 than tumors from normoglycemic or diabetic rats. A similar, but less pronounced, pattern of changes in IGFBP-3 mRNA was seen, whereas levels of IGFBP-6 mRNA were unchanged throughout. To identify the cell type producing the mRNAs for these IGFBPs, in situ hybridization of tissue sections was used. Procedures were established that localized three of the five IGFBPs expressed in this tumor tissue. This technique showed that IGFBP-3 mRNA transcripts were observed mainly in endothelial cells of tumor vasculature, although they were also detected in stromal cells, IGFBP-4 was present mainly in tumor stroma cells, and IGFBP-5 mRNA was expressed predominantly in the epithelial cells of this tumor. Expression of IGFBP-5 mRNA transcripts was significantly diminished in primary and long term cultured R3230AC cells grown in alpha-Minimum Essential Medium and 10% fetal bovine serum. Tumors arising from injection of long term cultured cells that were injected into isologous rats contained high amounts of mRNA transcripts for IGFBP-5, suggesting the presence, in vivo, of positive regulators for the expression of this BP. Tumor cells cultured in the presence of insulin displayed a 2.2- to 2.5-fold increase in the expression of IGFBP-5. These findings imply a role for insulin as a regulator of the expression of IGFBP-5 in the R3230AC adenocarcinoma.
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PMID:Insulin-like growth factor-binding proteins in R3230AC mammary tumors of intact and diabetic rats. 769 88

Angiogenesis is a key process in a variety of human diseases, including cancer. The ability to target selectively the tumor vasculature is potentially useful for the diagnosis and treatment of cancer. Still, little information is available regarding markers that are restricted to the ECs of tumor vessels. cDNA array technology allows simultaneous analysis of relative expression levels of a broad spectrum of genes in 2 related cell populations. We used this technology with the aim of identifying markers specific for TECs. TECs were isolated by CD31-mediated immunomagnetic separation from tumors induced by s.c. injection of NF9006 breast carcinoma cells into syngeneic mice. NECs were isolated from lactating mammary glands. The endothelial nature of isolated cells was confirmed by RT-PCR using CD31-specific primers and by uptake of DiI-Ac-LDL. Macrophage contamination in the EC isolations could be reasonably ruled out by assessing the expression of the macrophage marker c-fms. (32)P-labeled cDNA probes generated by reverse transcription from total RNA were hybridized to mouse-specific gene arrays. Several genes consistently showed differential expression between TECs and NECs. However, expression of only 1 of these genes, IGFBP-3, was restricted exclusively to ECs. Semiquantitative RT-PCR revealed 22- to 33-fold differential expression of IGFBP-3 in the TEC fraction. IGFBP-3 was overexpressed by a factor of 5 in an additional mouse model of breast carcinoma induced by 4T1.2 tumor cells. These results indicate that IGFBP-3 is a potential novel marker of angiogenesis. Elucidation of its role in tumor neovascularization may open the possibility of IGFBP-3 as a therapeutic target for antiangiogenesis.
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PMID:Insulin-like growth factor binding protein-3 is overexpressed in endothelial cells of mouse breast tumor vessels. 1249 64