Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many oncogene products have been shown to bear strong homology to or to interact with components of normal cellular signal transduction. We have previously shown that a glycoprotein band of 95 kilodaltons (kDa) becomes tyrosine phosphorylated in chick cells transformed by Rous sarcoma virus and that tyrosine phosphorylation of this protein band correlates tightly with phenotypic transformation in cells infected with a large and diverse panel of src mutants (L. M. Kozma, A. B. Reynolds, and M. J. Weber, Mol. Cell. Biol. 10:837-841, 1990). In this communication, we report that a component of the 95-kDa glycoprotein band is related or identical to the 95-kDa beta subunit of the receptor for insulinlike growth factor I (IGF-I). We found that the beta subunit of the IGF-I receptor comigrated on polyacrylamide gels with a component of the 95-kDa glycoprotein region from src-transformed cells under both reducing and nonreducing gel conditions and had a very similar partial phosphopeptide map. To further test the hypothesis that the beta subunit of the IGF-I receptor becomes tyrosine phosphorylated in cells transformed by pp60src, a human cell line that expressed the IGF-I receptor was transformed by src. Comparison of IGF-I receptors immunoprecipitated from normal and transformed cells revealed that the beta subunit of the IGF-I receptor became constitutively tyrosine phosphorylated in src-transformed cells. Moreover, IGF-I receptor phosphorylation induced by src was synergistic with that induced by the hormone: IGF-I-stimulated autophosphorylation of the receptor was much greater in src-transformed cells than in untransformed HOS cells even at maximal concentrations of IGF-I. This increased responsiveness to IGF-I was not due to increases in receptor number, time course of phosphorylation, or affinity for hormone. Finally, no IGF-I-like activity could be detected in culture supernatants collected from the src-transformed cells, suggesting that the increased receptor phosphorylation observed in the src-transformed cells may be mediated by an intracellular mechanism rather than an external autocrine stimulation. Our data demonstrate that the IGF-I receptor becomes constitutively tyrosine phosphorylated in src-transformed cells. This finding raises the possibility that pp60v-src alters growth regulation at least in part by phosphorylating and activating this growth factor receptor.
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PMID:Constitutive phosphorylation of the receptor for insulinlike growth factor I in cells transformed by the src oncogene. 216 77

The present study was undertaken to elucidate whether estriol (E3) affects the proliferative activity and the expression of insulin-like growth factor-I (IGF-I) mRNA and IGF-I receptor (IGF-IR) mRNA in cultured human osteoblast-like osteosarcoma cells (HOS TE85). In this study, the effects of E3 on cultured HOS TE85 cells were compared with those of 17 beta-estradiol (E2). HOS TE85 cells were subcultured in phenol red-free Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum for 72 h and then stepped down to serum-free conditions for an additional 72 h in the absence or presence of E3 (3.52 x 10(-9), 3.52 x 10(-8), 3.52 x 10(-7) mol/l) or E2 (3.67 x 10(-8) mol/l). Treatment with either E3 (3.52 x 10(-8), 3.52 x 10(-7) mol/l) or E2 (3.67 x 10(-8) mol/l) resulted in an increase in the number of cultured HOS TE85 cells and their uptake of bromodeoxyuridine. Northern blot hybridization with a IGF-I cDNA probe revealed that RNA prepared from cultured HOS TE85 cells contained IGF-I mRNA transcripts of 1.8, 4.4 and 7.5 kb. Treatment with either E3 (3.52 x 10(-9), 3.52 x 10(-8), 3.52 x 10(-7) mol/l) or E2 (3.67 x 10(-8) mol/l) resulted in increased expression of the three mRNA transcripts relative tot hose in untreated control cultures. Semi-quantitative, reverse transcription polymerase chain reaction analysis showed that the 440-bp IGF-IR mRNA transcript was present in HOS TE85 cells and that treatment with either E3 or E2 did not affect the IGF-IRmRNA expression in these cells. These results demonstrate that E3 (3.52 x 10(-9), 3.52 x 10(-8), 3.52 x 10(-7) mol/l) exerts profound effects on the proliferative potential of cultured HOS TE85 cells, compatible with that of E2 (3.67 x 10(-8) mol/l), through the induction of IGF-I mRNA expression without affecting IGF-IR mRNA expression in these cells.
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PMID:Effects of estriol on proliferative activity and expression of insulin-like growth factor-I (IGF-I) and IGF-I receptor mRNA in cultured human osteoblast-like osteosarcoma cells. 1596 40

The insulin-like growth factors I and II (IGF-I, IGF-II), their receptors, and high affinity binding proteins (IGFBPs) represent a family of cellular modulators that play essential roles in the development and differentiation of cells and tissues including the skeleton. Recently, the human osteosarcoma cell line HOS 58 cells were used as an in vitro model of osteoblast differentiation characterized by (i) a rapid proliferation rate in low-density cells that decreased continuously with time of culture and (ii) an increasing secretion of matrix proteins during their in vitro differentiation. In the present paper, HOS 58 cells with low cell density at early time points of the in vitro differentiation (i) displayed a low expression of IGF-I and -II; (ii) synthesized low levels of IGFBP-2, -3, -4, and -5, but (iii) showed high expression levels of both the type I and II IGF receptors. During the in vitro differentiation of HOS 58 cells, IGF-I and -II expressions increased continuously in parallel with an upregulation of IGFBP-2, -3, -4, and -5 whereas the IGF-I receptor and IGF-II/M6P receptor mRNA were downregulated. In conclusion, the high proliferative activity in low cell density HOS 58 cells was associated with high mRNA levels of the IGF-IR, but low concentrations of IGFBP-2. The rate of proliferation of HOS 58 cells continuously decreased during cultivation in parallel with a decline in IGF-IR expression, but increase of mitoinhibitory IGFBP-2. These data are indicative for a role of the IGF axis during the in vitro differentiation of HOS 58 cells.
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PMID:Alteration of the insulin-like growth factor axis during in vitro differentiation of the human osteosarcoma cell line HOS 58. 1737 31