Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously established transplantable rat thyroid carcinoma cell lines in vivo from primary thyroid tumors induced by N-bis-(2-hydroxypropyl)nitrosamine (DHPN). In the present study, an insulin-like growth factor I (IGF-I)-responsive cell line (TRTC-G1-C-A4) in culture was derived from one (well differentiated papillary type) of these carcinoma cell lines G1. TRTC-G1-C-A4 cells were found to exhibit specific saturable binding of IGF-I with a Kd of 1.16 nM at approximately 43.6 fmol/10(5) cells. Inclusion of IGF-I (10 and 50 ng/ml) in the culture medium resulted in a significant increase of [3H]thymidine incorporation and marked cell proliferation. IGF-II (10 ng/ml) and insulin (1 microgram) produced no such effects. The molecular weight of IGF-I receptors on the cell membrane was determined by Western blotting analysis, a single band of binding proteins with a molecular weight of 125 kDa being evident under non-reducing conditions. Reverse transcriptase polymerase chain reaction (RT-PCR) showed that the TRTC-G1-C-A4 cells contained IGF-I receptor mRNA with a sequence corresponding to that determined from rat uterus. These results demonstrate that the IGF-I receptor can be expressed in a thyroid carcinoma with an important contribution to cell growth.
 ...
PMID:Establishment of a rat thyroid carcinoma cell line in vitro demonstrating high DNA synthesis in response to insulin-like growth factor I. 862 Apr 77

Insulin-like growth factors, IGF-I and IGF-II, are potent regulators of oligodendrocyte development. Most of the IGF present in vivo is bound to members of a family of six high-affinity IGF-binding proteins (IGFBPs), which can either potentiate or inhibit IGF action, depending on other conditions. Additionally, serum contains a structurally unrelated protein, acid-labile sub-unit (ALS), which forms a ternary complex with IGF and IGFBP3. In this study, we used reverse-transcriptase polymerase chain reaction (RT-PCR) to examine the expression of mRNAs for IGFBP 1-6 and ALS in purified populations of oligodendroglial cells and astrocytes. We found that astrocytes express all six IGFBPs. A2B5+/O4- oligodendrocyte precursors, O4+/O1- intermediate precursors, and O1+ oligodendrocytes express IGFBP3, 5, and 6, while IGFBP4 is expressed in oligodendrocyte precursors but not at more mature stages. We were unable to detect ALS mRNA in whole brain or in cultured oligodendroglial cells. The presence of differentially expressed IGFBPs in developing oligodendrocytes and astrocytes could significantly affect the biological activity of IGF-I and IGF-II in the central nervous system and the IGF-responsiveness of the IGFBP-expressing cells.
 ...
PMID:Expression of insulin-like growth factor-binding protein messenger RNAs in developing rat oligodendrocytes and astrocytes. 941 60

Age-related bone loss is thought to be due to impaired osteoblast functions. Insulin-like growth factors (IGFs) have been shown to be important stimulators of bone formation and osteoblast activities in vitro and in vivo. We tested the hypothesis that in vitro osteoblast senescence is associated with changes in components of the IGF-system including IGF-I, IGF-II, IGF-binding proteins (IGFBPs) and IGFBP-specific proteases. We employed a human diploid osteoblast cell line obtained from trabecular bone explants and that exhibit typical characteristics of in vitro senescence during serial subculturing. Using a non-competitive reverse-transcriptase polymerase-chain reaction (RT-PCR) assay, we found that the constitutive level of IGF-I mRNA decreased progressively to 49.9 +/- 4.9% in old osteoblasts as compared to the levels found in the young cells. No age-related change was found in IGF-II steady-state mRNA levels. Changes in IGFBPs gene expression and protein production were assessed using Northern blot analysis and Western ligand blotting (WLB), respectively. IGFBP-3 mRNA levels decreased to 30% and protein production to 16% in aged osteoblasts as compared to levels found in young cells. We also found age-related decreases in mRNA levels of both IGFBP-4 and IGFBP-5 to 70% and 60% in aged osteoblasts, respectively, compared to young cells. While IGFBP-5 protein was not detected by WLB, IGFBP-4 protein production showed a biphasic change with 50% decrease in middle-aged cells and a subsequent increase in aged osteoblasts to levels similar to those in young osteoblasts. We found an age-related increase in the immunoreactive levels of IGFBP-4 protease, however, no detectable IGFBP-4 or IGFBP-3 protease activities in conditioned media from osteoblast cultures were observed. Our findings demonstrate that osteoblast aging is associated with impaired production of the stimulatory components of the IGF-system, that may be a mechanism contributing to age-related decline in osteoblast functions.
 ...
PMID:Changes in the insulin-like growth factor-system may contribute to in vitro age-related impaired osteoblast functions. 1112 90

Testis tumors occur frequently in dogs. The main types of tumors are Sertoli cell tumors, seminomas, and Leydig cell tumors. Mixed tumors and bilateral occurrence of tumors may be encountered frequently. To elucidate the possible relationship between the insulin-like growth factor (IGF) system and the development of different types of testis tumors in dogs, the expression of insulin-like growth factor-I and II (IGF-I and IGF-II), their type I receptor (IGF-IR), and their binding proteins (IGFBPs) was examined. In addition the expression of the steroidogenic enzymes p450-aromatase and 5alpha-reductase type I and type II, and the androgen receptor (AR) was investigated by a semiquantitative reverse-transcriptase PCR (RT-PCR). Both normal testes and testes with tumors were studied. In normal testes a clear expression of IGF-I, IGF-II, IGF-IR, IGFBP2, IGFBP4 and IGFBP5 was found. Expression of IGFBP1 and IGFBP3 was weak. There was also clear expression of the steroidogenic enzymes 5alpha-reductase, aromatase, and the AR. Quantification of RT-PCR products revealed significantly less expression of IGFBP1, IGF-I, and 5alpha-reductase type I in Sertoli cell tumors and seminomas. Leydig cell tumors and mixed tumors had a significantly higher expression of IGFBP4 and IGF-IR than normal testes. The expression of aromatase was lower in seminomas and in mixed tumors. The expression of AR, IGF-II and IGFBP2, IGFBP3, IGFBP5, and 5alpha-reductase type II did not differ among the different types of tumors. It was concluded that Sertoli cell tumors and seminomas have a comparable expression of the IGF system while Leydig cell tumors have a different pattern, suggesting difference in pathobiology among these types of tumors.
 ...
PMID:Expression of the insulin-like growth factor (IGF) system and steroidogenic enzymes in canine testis tumors. 1264 54

Conjugated linoleic acid (CLA) has chemoprotective properties in a variety of experimental cancer models. We have previously observed that dietary CLA inhibits colon tumorigenesis induced by 1,2-dimethylhydrazine in rats. In addition, our in vitro studies have shown that CLA inhibits DNA synthesis and induces apoptosis in HT-29 cells, the human colon adenocarcinoma cell line. The insulin-like growth factor (IGF) system regulates the growth of HT-29 cells by an autocrine mechanism. The present study examined whether the growth inhibitory effect of CLA is related to changes in the IGF system in HT-29 cells. To determine whether CLA inhibits IGF-II production, HT-29 cells were incubated in serum-free medium in the presence of various concentrations of CLA. CLA decreased protein levels of both mature and pro IGF-II and IGF-II transcripts. Whereas exogenous IGF-I and IGF-II produced an increase in cell number, neither IGF-I nor IGF-II counteracted the negative growth regulatory effect of CLA. Reverse transcriptase-polymerase chain reaction and Western blot analysis of total cell lysates revealed that CLA decreased IGF-I receptor (IGF-IR) transcript and protein levels in a dose-dependent manner. Immunoprecipitation/Western blot studies revealed that CLA inhibited IGF-I-induced phosphorylation of IGF-IR and insulin-receptor substrate (IRS)-1, recruitment of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K) to IGF-IR, IGF-IR-associated PI3K activity, and phosphorylated Akt and extracellular signal-regulated kinase (ERK)-1/2 levels. In conclusion, the inhibition of cell proliferation and induction of apoptosis by CLA in HT-29 cells may be mediated in part by its ability to decrease IGF-II synthesis and to downregulate IGF-IR signaling and the PI3K/Akt and ERK-1/2 pathways.
 ...
PMID:Conjugated linoleic acid downregulates insulin-like growth factor-I receptor levels in HT-29 human colon cancer cells. 1288 57