Dataset Information

Treatment of murine breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor decreases the level of plasminogen activator transcripts, inhibits cell growth in vitro, and reduces tumorigenesis in vivo.

ABSTRACT: AIMS:To establish that cells from the murine mammary carcinoma cell line, EMT6, express type I insulin-like growth factor receptor (IGF-IR), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA). To investigate the role of IGF-IR in growth, transformation, and tumorigenesis in addition to its relation to tPA and uPA in EMT6 cells. To assess the suitability of the EMT6/syngeneic mouse model for studying the role of IGF-IR in tumorigenesis. METHODS:The presence of transcripts for IGF-IR, tPA, and uPA was determined by northern blot analysis using poly (A(+)) RNA derived from EMT6 cells transfected with an antisense IGF-IR construct or a construct lacking the antisense IGF-IR insert. Flow cytometry was used to measure IGF-IR protein. Assays were performed to determine cell proliferation, transformation, and the tumorigenicity of antisense IGF-IR transfected EMT6 cells and control transfected EMT6 cells. RESULTS:There was strong expression of IGF-IR, tPA, and uPA in EMT6 cells. EMT6 cells from clones carrying antisense IGF-IR displayed a significant decrease in cell proliferation and lost the ability to form colonies in soft agar. A decrease in tumour size occurred when cells carrying the antisense IGF-IR were injected into syngeneic mice. Reduced expression of tPA and uPA was seen in EMT6 cells carrying the antisense IGF-IR construct. CONCLUSIONS:The IGF-IR plays a role in the progression, transformation, and tumorigenesis of EMT6 murine mammary carcinoma cells. The suppression of IGF-IR mRNA in EMT6 cells decreases tPA and uPA expression. EMT6 cells and the syngeneic mouse provide a suitable model for studying the role of IGF-IR in breast tumour progression.

SUBMITTER: Chernicky CL

PROVIDER: S-EPMC1187158 | biostudies-literature | 2002 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Treatment of murine breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor decreases the level of plasminogen activator transcripts, inhibits cell growth in vitro, and reduces tumorigenesis in vivo.

Chernicky C L CL Tan H H Yi L L Loret de Mola J R JR Ilan J J

Molecular pathology : MP 20020401 2

<h4>Aims</h4>To establish that cells from the murine mammary carcinoma cell line, EMT6, express type I insulin-like growth factor receptor (IGF-IR), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA). To investigate the role of IGF-IR in growth, transformation, and tumorigenesis in addition to its relation to tPA and uPA in EMT6 cells. To assess the suitability of the EMT6/syngeneic mouse model for studying the role of IGF-IR in tumorigenesis.<h4>Methods</h4> ...[more]

PMID: 11950959

Similar Datasets

Project description:BackgroundEmx2 encodes for a transcription factor expressed in the embryonic intermediate mesoderm and central nervous system (CNS). It is implicated in several aspects of cerebral cortex development, including morphogenetic field specification, arealization, precursor proliferation and lamination. Four Emx2-associated antisense transcripts have been found in the urogenital system; one of them, Emx2OS, has been also detected in the adult brain. Until now, however, nothing is known about expression and function of Emx2OS in the developing CNS.Methodology/principal findingsBy quantitative RT-PCR and in situ hybridization, we reconstructed the Emx2OS expression profile in the embryonic CNS, paying special attention to the developing cerebral cortex. Emx2OS was observed in a number of CNS structures expressing also Emx2. Within the cortex, Emx2OS was detectable in periventricular precursors, expressing the sense transcript, and peaked in newly born post-mitotic neurons not expressing such transcript. By integrating lentiviral gene delivery, RNAi, TetON technology, morpholino-mediated gene knock-down, drug-induced perturbation of gene expression, and quantitative RT-PCR, we addressed possible roles of Ex2 antisense RNA in Emx2 regulation, in primary CNS precursor cultures. We found that, in both cortical precursors and their neuronal progenies, Emx2 antisense RNA contributes to post-transcriptional down-regulation of its sense partner, possibly by a Dicer-promoted mechanism. The same RNA, when delivered to rhombo-spinal precursors, stimulates ectopic expression of Emx2, whereas Emx2 knock-out dramatically impairs Emx2OS transcription. This suggests that, within the developing CNS, a reciprocal Emx2/Emx2OS regulatory loop may normally sustain transcription at the Emx2 locus.Conclusions/significanceThis study shows that antisense transcripts may contribute to developmental regulation of a key transcription factor gene implicated in CNS patterning, possibly by complex and multilevel mechanisms. The activation of Emx2 by a short antisense transcript may be a prototype of a method for overexpressing single specific genes, without introducing additional copies of them into the genome.

Project description:ObjectivePlasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor that promotes and inhibits cell migration, plays a complex and important role in adverse vascular remodeling. Little is known about the effects of pharmacological PAI-1 inhibitors, an emerging drug class, on migration of vascular smooth muscle cells (SMCs) and endothelial cells (ECs), crucial mediators of vascular remodeling. We investigated the effects of PAI-039 (tiplaxtinin), a specific PAI-1 inhibitor, on SMC and EC migration in vitro and vascular remodeling in vivo.Approach and resultsPAI-039 inhibited SMC migration through collagen gels, including those supplemented with vitronectin and other extracellular matrix proteins, but did not inhibit migration of PAI-1-deficient SMCs, suggesting that its antimigratory effects were PAI-1-specific and physiologically relevant. However, PAI-039 did not inhibit EC migration. PAI-039 inhibited phosphorylation and nuclear translocation of signal transducers and activators of transcription-1 in SMCs, but had no discernable effect on signal transducer and activator of transcription-1 signaling in ECs. Expression of low-density lipoprotein receptor-related protein 1, a motogenic PAI-1 receptor that activates Janus kinase/signal transducers and activators of transcription-1 signaling, was markedly lower in ECs than in SMCs. Notably, PAI-039 significantly inhibited intimal hyperplasia and inflammation in murine models of adverse vascular remodeling, but did not adversely affect re-endothelialization after endothelium-denuding mechanical vascular injury.ConclusionsPAI-039 inhibits SMC migration and intimal hyperplasia, while having no inhibitory effect on ECs, which seems to be because of differences in PAI-1-dependent low-density lipoprotein receptor-related protein 1/Janus kinase/signal transducer and activator of transcription-1 signaling between SMCs and ECs. These findings suggest that PAI-1 may be an important therapeutic target in obstructive vascular diseases characterized by neointimal hyperplasia.

Dataset Information

Treatment of murine breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor decreases the level of plasminogen activator transcripts, inhibits cell growth in vitro, and reduces tumorigenesis in vivo.

Publications

Treatment of murine breast cancer cells with antisense RNA to the type I insulin-like growth factor receptor decreases the level of plasminogen activator transcripts, inhibits cell growth in vitro, and reduces tumorigenesis in vivo.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets