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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that the insulin-like growth factor-2 (IGF-2) gene is partially coexpressed with the IGF-1 and -2 receptor genes in proliferative cytotrophoblasts of the human extraembryonic tissue. Here we show that high levels of IGF-2 gene expression are not restricted to the embryonic tissue but can also be found in the decidua compacta. The IGF-2 gene is thus expressed at high levels in the mesenchymal stroma of the decidua to establish potentially short-range communication with primarily IGF-1 receptor-positive mesenchymal stroma cells. Conversely, the glandular and surface epithelia coexpress the IGF-1 receptor and IGF-1 genes, while the IGF-2 gene is not detected above background levels. The potential control mechanisms of these cell-cell signalling pathways were investigated by the analysis of the spatial distribution of active IGF binding proteins (IGFBP) genes. The IGFBP-3 gene is coexpressed with the IGF-2 gene in proliferative cytotrophoblasts of the embryonic placenta. While active IGFBP-1 and -2 genes in our hands cannot be detected in the embryonic placenta, all three IGFBP genes are expressed in complex and overlapping patterns in the decidua compacta. The results are discussed in terms of how the various IGFBP genes may operate in different cell types to restrict IGF local stimulatory pathways.
Mol Reprod Dev 1992 Sep
PMID:Spatial distribution of active genes implicated in the regulation of insulin-like growth factor stimulatory loops in human decidual and placental tissue of first-trimester pregnancy. 138 Aug 18

Because recent studies have particularly implicated the insulin growth factor family in early development, the effects of insulin-like growth factor (IGF-1) on the development of mouse embryos in vitro were investigated in detail. When added to the medium for culture of two-cell embryos, IGF-1 stimulated the number of cells in the resultant blastocysts after 54 hr, entirely by increasing the number of cells in the inner cell mass (ICM) (16.0 +/- 0.5 vs. 12.6 +/- 0.5 cells/ICM). This stimulation was also achieved when ICMs were isolated from blastocysts prior to culture for 24 hr with IGF-1 (22.3 +/- 1.0 vs. 17.5 +/- 0.8 cells/ICM). There was no effect on IGF-1 on trophectoderm (TE) cell proliferation. In morphology studies, IGF-1 also increased the proportion of blastocysts (62% +/- 3% vs. 49% +/- 4%) while decreasing the number of embryos remaining as morulae (32% +/- 3% vs. 38% +/- 2%) or in the early cleavage stages (7% +/- 3% vs. 13% +/- 3%) after 54 hr culture from the two-cell stage. All these effects were achieved with EC50s of approximately 60 pM IGF-1, which is in the range for IGF-1 receptor mediation; however, cross reaction with insulin, IGF-2, or other unknown receptors is not excluded. Nonetheless, the results show that physiological concentrations of IGF-1 (17-170 pM, 0.1-1 ng/ml), which have been observed in the reproductive tract, affect the early embryo, suggesting a normal role for this factor in the regulation of growth of the developing conceptus before implantation.
Mol Reprod Dev 1992 Mar
PMID:Insulin-like growth factor-1 stimulates growth of mouse preimplantation embryos in vitro. 155 4

The liver is an epithelioid organ that can regenerate following partial hepatectomy. Although it is composed mainly of hepatocytes, it has a complex, multicellular architecture, implying that intercellular communications must exist during regeneration. As in other mitogen-stimulated cells, immediate-early growth response genes induced in the absence of prior protein synthesis are likely to play an important regulatory role in the regenerative process. Through differential screening of regenerating liver cDNA libraries, we found that one of the most highly expressed immediate-early genes in liver regeneration encodes the rat homolog of the low-molecular-weight insulinlike growth factor (IGF)-binding protein (IGFBP-1). This protein has been implicated in enhancing the mitogenic effect of IGF on tissues. IGFBP-1 gene induction is transcriptionally mediated and specific to regenerating liver, as the gene is not expressed in mitogen-stimulated fibroblasts. IGFBP-1 expression has been shown to increase under low-insulin conditions such as diabetes, and the complex regulation of expression is indicated by our finding that insulin treatment of H35 rat hepatoma cells, which induces proliferation, also causes a rapid decrease in transcription and expression of the IGFBP-1 gene. Of note, IGFBP-1 mRNA is abundant in fetal rat liver, implying that it participates in normal liver growth and development. Although regenerating liver cells continue to produce IGF-I, we did not detect IGF-I receptor mRNA during the first 24 h after hepatectomy. However, some IGFBPs may act to enhance the activity of IGF-I independently of IGF-I receptors. Thus, IGF-1 and IGFBPs may interact with hepatocytes or nonparenchymal liver cells, through either IGF-I or novel receptors. In this way, IGFBP-I and IGF-I could act in a paracrine and/or autocrine fashion in maintaining normal liver architecture during regeneration.
Mol Cell Biol 1991 Mar
PMID:The gene encoding rat insulinlike growth factor-binding protein 1 is rapidly and highly induced in regenerating liver. 170 4

Insulin specifically stimulates protein synthesis in compacted mouse embryos on days 3 and 4 after fertilization, with an EC50 of 0.5 pM (Harvey and Kaye, 1988). The identity of the receptor mediating this short-term effect of insulin was further examined by dose-response studies with IFG-1 and by using a specific anti-insulin receptor antiserum that has no appreciable cross-reaction with IGF-1 receptors. IGF-1 caused a maximum 40% stimulation of protein synthesis after 4 h exposure (similar to the response to insulin) with an EC50 of 150 pM IGF-1. The insulin receptor-specific antiserum, or IgGs isolated from it, also stimulated protein synthesis at dilutions as high as 1:1,000 to the same degree as insulin (approximately 40%). This agonistic action of the insulin receptor antiserum, the EC50 of 150 pM for IGF-1, and the previously established EC50 of 0.5 pM for insulin, all with similar maximal stimulation, strongly support the conclusion that the short-term metabolic stimulation of mouse blastocysts by insulin is mediated by insulin receptors. Immunosurgical isolation of inner cell masses before and after exposure to 1.7 pM insulin (sufficient to stimulate only the insulin receptor) showed that insulin stimulates protein synthesis in these cells as well as in the trophectoderm cells of the blastocyst. This finding suggests that in intact blastocysts, insulin may travel across the trophectoderm to the inner cell mass, acting anabolically on both tissues. Analysis of the agonistic effect of the B-10 antiserum showed there was no evidence of an unresponsive subpopulation of embryos.
Mol Reprod Dev 1991 Jul
PMID:Mouse blastocysts respond metabolically to short-term stimulation by insulin and IGF-1 through the insulin receptor. 193 Oct 41

Sertoli cell conditioned medium (SCCM) contains a potent mitogen, Sertoli cell secreted growth factor (SCSGF). A431 cells, derived from a human epidermoid carcinoma have provided an excellent model cell line for the study of this apparently unique activity secreted by rat Sertoli cells in vitro. Previously, it was shown that SCCM contained an epidermal growth factor (EGF)-like activity which was thought to be the mitogen for A431 cells. The present study showed that these two factors are distinct entities. The secretion of the EGF-like activity decreased with increasing number of culture days, while that of SCSGF and of another Sertoli cell specific protein, transferrin remained constant. The addition of SCCM stimulated whereas 2.5 ng/ml EGF inhibited the A431 cell growth. The proliferative response of A431 cells to a wide variety of growth factors and known Sertoli cell secretions was investigated. SCSGF was the only growth factor of known Sertoli cell secretions tested (transforming growth factors (TGF alpha, TGF beta), EGF, bombesin, fibroblast growth factor (FGF), platelet derived growth factor (PDGF), insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), prostaglandins E-1 and E-2, insulin, transferrin and lactate) which stimulated A431 cell proliferation. SCSGF was mitogenic for A431 cells even in the presence of serum in the culture medium. The partially purified SCSGF was heat- and acid-stable, protease-sensitive with a molecular weight of 14,000. It did not bind to heparin or concanavalin A-Sepharose. The secretion of a mitogenic activity by the Sertoli cell which is different from other previously identified growth factors and which coincides with active spermatogenesis could have important implications in the regulation of spermatogenesis.
Mol Cell Endocrinol 1991 Aug
PMID:Partial characterization of a unique mitogenic activity secreted by rat Sertoli cells. 193 36

The prognostic value of EGF-R, IGF-1-R and SS-R, and of cytosolic estrogen-regulated pS2 protein, was studied in patients (pts) with primary breast and advanced ovarian cancer. Ovarian cancer tissues were negative for pS2 (by immunoradiometric assay) IGF-1-R and EGF-R contents (by ligand binding assay, LBA) were of no or moderate prognostic value for breast cancer pts (n = 214). For advanced ovarian cancer pts, EGF-R content determined by LBA (n = 55) showed no prognostic value, whereas EGF-R status (n = 35) determined by immunohistochemistry (MoAb 2E9) significantly correlated with progression of disease (P less than 0.05). In breast cancer pts, both SS-R and pS2 showed no association with tumor size, nodal status and grade. For pS2 the best cut-off level with respect to relapse-free (RFS) and overall survival (OS) was found to be 11 ng/mg protein. Both SS-R (1 g% SS-R+, n = 135; P less than 0.04) and pS2 (27% pS2+, n = 197; P less than 0.001), which were mainly positive in ER+ tumors, were of prognostic value, especially within the subgroups with ER+/PgR+ tumors. Also within N+ and No pts the 5-yr RFS and OS showed a difference between pS2+ and pS2- (33 and 54% for N+, and 31 and 13% difference for No pts). In summary, SS-R and pS2 are valuable prognosticators in breast cancer pts, and prognostic significance of EGF-R in ovarian cancer pts needs further study.
J Steroid Biochem Mol Biol 1990 Dec 20
PMID:Prognostic value of pS2 protein and receptors for epidermal growth factor (EGF-R), insulin-like growth factor-1 (IGF-1-R) and somatostatin (SS-R) in patients with breast and ovarian cancer. 217 64

The insulin-like growth factor I (IGF-1) mediates the actions of pituitary growth hormone in a variety of tissues. Its receptor (IGF1R) displays considerable structural similarity to the insulin receptor. In humans, the IGF1R gene has been mapped near FES, the cellular counterpart of the feline sarcoma virus transforming gene v-fes, at the q25-q26 region of human chromosome 15 (HSA15). Here, we report the mapping of mouse Igf1r to mouse chromosome 7 (MMU7) by somatic cell hybrid analysis. This result, along with the prior assignment of the loci for mitochondrial isocitrate dehydrogenase and FES to human chromosome 15 and mouse chromosome 7, suggest a conserved autosomal synteny group on the distal long arm of HSA15 and in the center of MMU7.
Somat Cell Mol Genet 1989 Jul
PMID:Insulin-like growth factor I receptor gene is concordant with c-Fes protooncogene and mouse chromosome 7 in somatic cell hybrids. 254 93

Phorbol esters bind to and activate a family of Protein Kinase C (PKC) proteins, although the degree to which the various PKC forms mediate specific biological functions is unknown. We and others have previously shown that, after exposure to phorbol esters, cultured fibroblasts exhibit increased expression of the mRNA encoding the HepG2/brain glucose transporter (GT mRNA). We therefore studied phorbol ester regulation of GT mRNA in rat fibroblasts which do (R6-PKC3) or do not (R6-C1) stably overproduce a full-length cDNA encoding the PKC beta 1 isotype. When PKC beta 1 is overproduced in a cell that normally has undetectable levels, it is capable of increasing HepG2/brain GT mRNA in response to alpha-D-glucose phorbol 12-myristate 13-acetate (TPA). The level of GT mRNA is maximally induced 6 to 8-fold over basal levels 6 h after exposure to TPA (10 ng/ml) in R6-PKC3 cells that overproduce PKC beta 1, but only 2-fold over basal levels in the control R6-C1 cells. This TPA induced increase in the level of GT mRNA was observed as early as 1 h, peaked by 6-8 h and decreased markedly by 24 h in both cell types. The effect of PKC beta 1 on GT mRNA expression is probably mediated through enhancement of transcription, since the stability of GT mRNA was only minimally affected by TPA. Unlike the enhancement of TPA induced GT mRNA expression caused by overexpression of PKC beta 1, the responses of GT mRNA to calf serum, platelet-derived growth factor, epidermal growth factor, insulin or insulin-like growth factor-1 were the same in both cell types. After pretreatment with 1000 ng/ml TPA in 0.5% calf serum for 24 h, PKC activity was down-regulated and both R6-C1 and R6-PKC3 cells showed complete down-regulation of the GT mRNA responses to an additional treatment with 1000 ng/ml TPA. In contrast to the marked loss of responsiveness to TPA and PKC down-regulation, the responses of GT mRNA to serum, PDGF, EGF, insulin and IGF-1 were unaffected by down-regulation. Thus, our results provide direct evidence for both PKC-dependent and independent pathways regulating GT gene expression. Furthermore, it appears that the level of PKC beta 1 production, rather than down-stream signal transduction events, is the rate-limiting step in the pathway by which TPA induces an increase in GT mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Endocrinol 1989 Dec
PMID:Overproduction of the beta 1 form of protein kinase C enhances phorbol ester induction of glucose transporter mRNA. 262 36

Poor growth in diabetes involves low circulating levels of somatomedins/insulin-like growth factors (IGFs), largely reflecting decreased growth factor release by the liver. To define regulatory mechanisms, circulating IGF-1 was compared with levels of a high mol wt putative hepatic IGF-1 precursor and hepatic IGF-1 mRNA in a model of progressive severity of diabetes in rats. Streptozotocin administered at 36, 72, 144, and 288 mg/kg produced graded metabolic decompensation 2 days later, from minimal hyperglycemia with continued weight gain at 36 mg/kg, to marked hyperglycemia, ketonemia, and weight loss at 288 mg/kg (all P less than 0.001). Total serum IGF-1 measured by RIA was unchanged with the 36 and 72 mg/kg doses of streptozotocin (471 +/- 19 and 439 +/- 27 ng/ml, respectively, vs. 517 +/- 27 ng/ml in controls) despite serum glucose greater than 400 mg/dl. With streptozotocin 144 and 288 mg/kg, serum IGF-1 fell to 131 +/- 27 and 142 +/- 10 ng/ml, respectively (both P less than 0.005 vs. controls). Serum IGF-1 was correlated strongly with serum beta-hydroxybutyrate and body weight (r = -0.88 and 0.91, respectively, P less than 0.0001), and less strongly with serum glucose (r = -0.59, P less than 0.0002). Extractable hepatic content of a high mol wt form of immunoreactive IGF-1 (a putative precursor) was unchanged at the two lowest doses of streptozotocin (68 +/- 4 and 83 +/- 9 ngeq/g vs. 67 +/- 4 in controls), but decreased to 16 +/- 3 and 29 +/- 4 ng/g at the two highest doses (both P less than 0.001 vs. controls).(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1988 Nov
PMID:Nutrition and somatomedin. XIX. Molecular regulation of insulin-like growth factor-1 in streptozotocin-diabetic rats. 297 56

The processing of LamB-IGF-1 fusion protein and the export of processed IGF-1 (insulin-like growth-factor-1) into the growth medium was examined in the Escherichia coli host strain, JM101. Several strain or plasmid modifications were tried to increase export of periplasmic (processed) IGF-1 into the growth medium of JM101. These included: (1) use of a lon null mutant strain to increase accumulation levels of unprocessed LamB-IGF-1 fusion protein; (2) use of an alternative drug resistance marker on the expression plasmid rather than beta-lactamase, thereby reducing any competition for processing of LamB-IGF-1 by signal peptidase; (3) examination of whether phage M13 gene III protein expression caused more periplasmic IGF-1 to be exported into the growth medium due to increased outer membrane permeability; and (4) examination of the effect of E. coli or yeast optimized IGF-1 codons. None of these strain or plasmid modifications caused any significant increase in export of IGF-1 into the growth medium of JM101. Solubility studies of LamB-IGF-1 and processed IGF-1 showed that virtually all of the LamB-IGF-1 and IGF-1 remaining within the cell after a 2 h induction period was insoluble. This implied that only soluble LamB-IGF-1 was processed to IGF-1 and that only soluble IGF-1 was exported into the growth medium. Taken together, the results indicated that LamB-IGF-1 and IGF-1 solubility were the limiting factors in secretion of IGF-1 into the periplasm and export of IGF-1 into the growth medium.
Mol Gen Genet 1988 Dec
PMID:Secretion and export of IGF-1 in Escherichia coli strain JM101. 307 40


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