Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.27.5 (RNase)
17,967 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat IGF-I mRNAs contain one of two alternative 5'-untranslated regions which are encoded by alternative exons (exons 1 and 2) and whose expression is controlled by alternative promoter elements. We investigated the ability of fragments of DNA which contain exon 1 and its 5'-flanking region to regulate transcription of a luciferase reporter gene in transient transfection assays. Maximal promoter activity was obtained with a construct which contained 412 bp of 5'-flanking region, while constructs which contained 1120 and 1690 bp of 5'-flanking region induced approximately 50% less enzymatic activity. Mapping of transcription start sites by RNase protection assay demonstrated that native start sites were used by these constructs, although the relative use of different start sites was different from start site usage by the endogenous gene. These data demonstrate that the 5'-flanking region of exon 1 is capable of regulating transcription of IGF-I mRNAs.
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PMID:Characterization of a rat insulin-like growth factor I gene promoter. 147 69

Insulin-like growth factor (IGF) I is a polypeptide hormone important in normal growth and development. Although IGF-I is a mitogen for many cancer cell lines, previous work has suggested that autocrine production of IGF-I is uncommon in cancers of epithelial origin. In this study, expression of IGF-I, its binding proteins, and its receptor were examined in ovarian cancer cell lines and tissues. Of 10 ovarian cancer cell lines, 3 (OVCAR-3, OVCAR-7, and PEO4) expressed IGF-I mRNA. RNase protection assays using probes derived from IGF-IA, IGF-IB, and alternate exon 1 IGF-I complementary DNAs demonstrated that these cells contained a predominant IGF-I transcript with an alternate first exon. RNA extracted from primary and metastatic ovarian cancer tissues also expressed IGF-I mRNAs (7 of 7) with the alternate first exon. IGF-I protein was detected in OVCAR-3-conditioned media; this activity was secreted in conjunction with several IGF-binding proteins (IGFBPs). IGFBP-2, IGFBP-3, an Mr 24,000 species, and an Mr 30,000 species could also be demonstrated in OVCAR-3. Type I IGF receptor mRNA was found in all 10 of the ovarian cancer cell lines and all 7 of the primary or metastatic ovarian cancer tissues. IGF-I was a mitogen for OVCAR-3, demonstrating the presence of a functional type I IGF receptor. These data show that all the necessary components for an IGF-I-mediated autocrine loop are expressed by ovarian cancer cells.
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PMID:Expression of insulin-like growth factor I, its binding proteins, and its receptor in ovarian cancer. 171 38

Rat IGF-I mRNAs contain two different 5'-UTR sequences as a result of alternate splicing of leader exons. Using a combination of solution hybridization/RNase protection and primer extension assays, we have mapped the transcriptional start sites in these leader exons. There appear to be three putative transcription start sites in exon 1 spread over a 140-bp region, the most upstream of which defines a 381 bp-long exon 1. There appear to be three distinct start sites in exon 2, the most upstream of which defines a greater than 770 bp-long exon 2. The two downstream start sites in exon 1 together account for approximately 70% of IGF-I gene expression in adult rat liver. Essentially all of the remaining IGF-I gene expression comes from the second start site in exon 2. Rat IGF-I gene transcription may therefore be regulated by two distinct promoter regions, a disperse promoter for exon 1, with several transcription initiation sites, and a more typical promoter region for exon 2, which controls transcription initiation from a discrete region.
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PMID:Transcription initiation in the two leader exons of the rat IGF-I gene occurs from disperse versus localized sites. 202 99

The insulin-like growth factors IGF-I and IGF-II are potent mitogens for several breast tumor cell lines in culture. Additionally, both IGF-I and IGF-II mRNAs are easily detected in the majority of breast tumor specimens examined, while no breast cancer epithelial cell lines we have studied express authentic IGF-I mRNA, and few lines express IGF-II mRNA. Although receptors for insulin, IGF-I, and IGF-II have been described, there is significant cross-reactivity between the various receptors and ligands in the insulin/insulin-like growth factor family, and it is not clear which receptor or receptors are responsible for the biological effects of these growth factors in this system. Using an RNase protection assay, we examined breast tumor specimens and breast cancer epithelial cell lines for expression of mRNA encoding the type I and type II IGF receptors as well as the insulin receptor. Virtually all of the specimens examined expressed mRNA for all three receptors. We then examined estrogen-dependent MCF-7 cells for the mitogenic effects of IGF-I and II in the presence of antibodies to both the type I and type II receptors. alpha IR-3, a monoclonal antibody which blocks the type I receptor, abolished the mitogenic effects of both IGF-I and IGF-II. It did not, however, block the mitogenic effects of insulin. We conclude that type I and type II IGF receptors are ubiquitously expressed in breast cancer, and our experiments with MCF-7 cells suggest the mitogenic effects of both IGF-I and IGF-II are mediated via the type I IGF receptor.
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PMID:Insulin-like growth factor receptor expression and function in human breast cancer. 215 73

The IGFs may be important autocrine, paracrine or endocrine growth factors for human breast cancer. IGF-I and II stimulate growth of cultured human breast cancer cells. IGF-I is slightly more potent, paralleling its higher affinity for the IGF-I receptor. Antibody blockade of the IGF-I receptor inhibits growth stimulation induced by both IGFs, suggesting that this receptor mediates the growth effects of both peptides. However, IGF-I receptor blockade does not inhibit estrogen (E2)-induced growth suggesting that secreted IGFs are not the major mediators of E2 action. Several breast cancer cell lines express IGF-II mRNA by both Northern analysis and RNase protection assay. IGF-II activity is found in conditioned medium by radioimmuno and radioreceptor assay, after removal of somatomedin binding proteins (BP) which are secreted in abundance. IGF-I is undetectable. BPs of congruent to 25 and 40 K predominate in ER-negative cell lines while BPs of 36 K predominate in ER-positive cells. Blockade of the IGF-I receptor inhibits anchorage-independent and monolayer growth in serum of a panel of breast cancer cell lines. Growth of one line (MDA-231) was also inhibited in vivo by receptor antibody treatment of nude mice. The antibody had no effect on growth of MCF-7 tumors. These data suggest that IGFs are important regulators of breast cancer cell proliferation and that antagonism of this pathway may offer a new treatment strategy.
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PMID:Regulation of breast cancer growth by insulin-like growth factors. 217 63

The insulin-like growth factors (IGFs) may be important autocrine and paracrine mediators of organ growth. We used solution-hybridization/ribonuclease protection assays to examine IGF-I and IGF-II mRNA abundance during hypertrophy or the rat adrenal gland induced by unilateral adrenalectomy or by adrenocorticotropic hormone (ACTH) infusion. Adrenal IGF-I mRNA did not change during the period of rapid organ growth at 18 or 66 h after unilateral adrenalectomy. ACTH infusion induced a time- and dose-dependent decrease in adrenal IGF-I mRNA despite significant increases in gland size. IGF-II mRNA also remained unchanged after unilateral adrenalectomy and decreased after ACTH infusion, to a greater extent than IGF-I mRNA. Liver IGF-I mRNA did not change with ACTH exposure, indicating an effect specific to the adrenal. We also measured adrenal P450scc mRNA as a marker of steroidogenic capacity. P450scc mRNA was unchanged after unilateral adrenalectomy and increased with ACTH infusion. Thus IGF-I and IGF-II mRNAs respond in parallel, but in different fashions with different stimuli for adrenal growth. The decrease in IGF mRNA after exposure to ACTH may be a factor in the ACTH-induced inhibition of compensatory hypertrophy after unilateral adrenalectomy.
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PMID:Rat insulin-like growth factor-I and -II mRNAs are unchanged during compensatory adrenal growth but decrease during ACTH-induced adrenal growth. 226 16

Insulin-like growth factor-II (IGF-II) is a potent mitogen for several types of cultured cells and tissues. We have studied the interaction of IGF-II with a panel of cultured human breast cancer cell lines, examining the possibility that these cells synthesize and secrete IGF-II activity which could have autocrine/paracrine functions. Synthetic IGF-II was mitogenic in five of seven cell lines tested, including the estrogen receptor-positive lines MCF-7L, ZR75-1, and T47D and the estrogen receptor (ER)-negative lines Hs578T and MDA-231. IGF-II was slightly less potent than IGF-I in stimulating DNA synthesis in MCF-71 cells, an effect that paralleled its ability to compete for [125I]IGF-I binding in these cells. Affinity labeling studies revealed that IGF-II could also compete for binding to the 130,000 mol wt alpha-subunit of the IGF-I receptor. A monoclonal antibody to the IGF-I receptor inhibited the mitogenic effects of IGF-II in MCF-7L and MDA-231 cells, suggesting that this receptor mediates the growth effects of IGF-II in these breast cancer cells. Using a RIA and a RRA, IGF-II-like activity was detected in conditioned medium extracts processed to remove IGF-binding proteins from several breast cancer cell lines, with the highest levels found in conditioned medium from MCF-7L and T47D cell lines. IGF-II mRNA transcripts in MCF-7L and T47D cells were identified by Northern blot analysis and were confirmed by RNase protection assay. IGF-II mRNA was increased by estrogen in MCF-7L cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin-like growth factor-II (IGF-II): a potential autocrine/paracrine growth factor for human breast cancer acting via the IGF-I receptor. 255 2

We, and others, have recently reported that the ovary is a site of insulin-like growth factor (IGF)I gene expression. It was the objective of the present studies to assess the relative ovarian abundance of IGF-I transcripts with alternative 5'-untranslated (UT) regions, their cellular localization, and hormonal regulation. To this end, a solution hybridization/RNase protection assay was employed wherein total rat ovarian RNA was hybridized with a 404-base 32P-labelled rat IGF-I riboprobe corresponding to the Class A 5'UT variant. As in liver, three protected bands [322 (Class A), 297 (Class B), and 242 (Class C) bases long] were noted, in keeping with established alternative 5' UT transcripts. The ovarian (as the hepatic) Class C variant proved the most abundant. The ovarian Class B variant was barely detectable. Cellular localization studies revealed these ovarian IGF-I transcripts to be primarily, if not exclusively, of granulosa but not theca-interstitial cell origin. Treatment of immature (21-23 days old) hypophysectomized rats with a diethylstilbestrol (DES)-containing subcutaneous silastic implant for a total of 5 days resulted in a 2-fold increase in the (densitometrically quantified) abundance of ovarian IGF-I transcripts, a diametrically-opposed effect (2.6-fold decrease) being noted at the level of the liver. Whereas treatment of hypophysectomized rats with oGH by itself (150 micrograms, qd, sc x5 days) resulted in a 5-fold increase in hepatic IGF-I gene expression, a limited, albeit distinct inhibitory effect was observed on the steady-state levels of ovarian IGF-I mRNA. In contrast, combined treatment with oGH and DES yielded a 3-fold increase in the abundance of ovarian IGF-I transcripts, there being no net alteration in hepatic IGF-I gene expression. Taken together, these findings reveal ovarian expression of the 3 known 5'-UT IGF-I mRNA variants, document the granulosa cell as the main somatic ovarian cell of IGF-I mRNA generation, and indicate that hepatic and ovarian IGF-I gene expression are differentially regulated in diametrically opposed directions.
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PMID:Rat ovarian insulin-like growth factor I (IGF-I) gene expression is granulosa cell-selective: 5'-untranslated mRNA variant representation and hormonal regulation. 273 67

We have employed Northern blot analyses and solution hybridization/RNase protection assays to evaluate the presence and stability of IGF-I mRNA splicing variants in the GH3 rat pituitary cell line. All of the IGF-I mRNA size classes and IGF-I mRNAs with alternately-spliced 5'-untranslated regions and E-peptide coding regions seen in adult rat liver also were present in GH3 cells, although the proportions of the 5' splicing variants were significantly altered. In actinomycin D-treated cells, all IGF-I mRNA splicing variants were equally stable; thus, changes in the levels of some splicing variants were not due to differential mRNA stability. Additionally, all IGF-I mRNA size classes seen on Northern blots were equally stable; this data suggests that the large IGF-I mRNA species is not a precursor of the smaller species.
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PMID:Expression and stability of insulin-like growth factor-I (IGF-I) mRNA splicing variants in the GH3 rat pituitary cell line. 276 27

Previous studies have shown that insulin-like growth factors (IGF-I and IGF-II) stimulate mitogenic activity in human endometrial stromal cells. In the present study, we have investigated the expression of IGF-I and -II mRNA to ascertain any autocrine growth-promoting effect in this system. Northern blot analysis revealed that endometrial stromal cells express multiple sizes of IGF-I and -II transcripts. The effect of progestin and antiprogestin was studied during decidualization of endometrial stromal cells in long-term culture. Solution hybridization and a ribonuclease protection assay of control cells revealed that the level of IGF-I mRNA was low, whereas IGF-II mRNA was always abundant. Medroxyprogesterone acetate (MPA) stimulated the expression of IGF-I mRNA > 4-fold in predecidualized cells during the first 10 days of culture. IGF-I mRNA decreased to basal level in prolonged culture when cells were decidualized. In contrast, MPA suppressed the IGF-II mRNA level by 60% in predecidualized cells, but IGF-II mRNA was highly expressed after 20 days of incubation with MPA (5-fold increase from Days 5-10 to Day 20 of culture). In progestin-pretreated cells, addition of the antiprogestin RU486 for 1-4 days reduced IGF-I mRNA by 50-90%. RU486 reversed the suppressive effect of MPA and increased IGF-II mRNA. This study indicates that progestin and antiprogestin differentially regulate IGF-I and IGF-II mRNA levels in human endometrial stromal cells.
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PMID:Progestin and antiprogestin differentially regulate the expression of insulin-like growth factors (IGF-I and IGF-II) messenger ribonucleic acid in human endometrial stromal cells. 749 87


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