Abstract
We have reported that human ovarian-carcinoma cell lines express high-affinity IL-4 receptor. Since IL-4R has been hypothesized to share a chain with IL-13R, we investigated whether ovarian cancer cells express IL-13 receptor. In the present study, we report that the ovarian-carcinoma cell lines IGROV-1 and PA-1 express varying numbers of high-affinity IL-13 receptors. Furthermore, IL-13 inhibited the binding of IL-4 on both ovarian-carcinoma cell lines, while IL-4 did not inhibit IL-13 binding on IGROV-1 cell line. IL-13 and IL-4 induced the phosphorylation of JAK1, JAK2 and Tyk2 Janus kinases in PA-1 cells. In contrast, JAK3 tyrosine kinase was expressed in PA-1 cells, but IL-4 or IL-13 did not augment its phosphorylation. In IGROV-1 cells, Tyk2 was constitutively phosphorylated and this phosphorylation was augmented by IL-4 or IL-13. JAK1 and JAK2 but not JAK3 were expressed but only JAK2 was faintly phosphorylated in response to either IL-13 or IL-4 respectively. IRS (insulin-receptor substrate)-1 and IRS-2 were also phosphorylated constitutively in both ovarian cancer cell lines examined, but only the phosphorylation of IRS-1 was augmented in response to IL-4 or IL-13. STAT6 was phosphorylated and activated in response to IL-4 and IL-13 in all cell lines examined. Our results demonstrate that ovarian cancer cell lines may express 2 types of IL-13R and the IL-13- or IL-4-induced signaling patterns may be slightly different in each type of receptor.
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology*
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Antigens, CD / biosynthesis*
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Antigens, CD / genetics
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Female
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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Insulin Receptor Substrate Proteins
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Interleukin-13 / pharmacology*
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Interleukin-13 Receptor alpha1 Subunit
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Interleukin-4 / pharmacology*
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Intracellular Signaling Peptides and Proteins
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Janus Kinase 1
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Janus Kinase 2
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Janus Kinase 3
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Neoplasm Proteins / biosynthesis*
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Neoplasm Proteins / genetics
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Ovarian Neoplasms / genetics
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / pathology*
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Phosphoproteins / metabolism
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Phosphorylation
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Protein Processing, Post-Translational / drug effects*
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins*
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Receptors, Interleukin / biosynthesis*
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Receptors, Interleukin / genetics
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Receptors, Interleukin-13
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Receptors, Interleukin-4
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STAT6 Transcription Factor
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Signal Transduction / drug effects*
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Teratocarcinoma / genetics
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Teratocarcinoma / metabolism
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Teratocarcinoma / pathology*
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Trans-Activators / metabolism
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Transcription Factors / metabolism
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Tumor Cells, Cultured / drug effects
Substances
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Antigens, CD
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IL13RA1 protein, human
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IRS1 protein, human
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IRS2 protein, human
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Insulin Receptor Substrate Proteins
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Interleukin-13
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Interleukin-13 Receptor alpha1 Subunit
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Intracellular Signaling Peptides and Proteins
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Neoplasm Proteins
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Phosphoproteins
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Proto-Oncogene Proteins
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Receptors, Interleukin
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Receptors, Interleukin-13
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Receptors, Interleukin-4
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STAT6 Transcription Factor
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STAT6 protein, human
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Trans-Activators
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Transcription Factors
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Interleukin-4
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Protein-Tyrosine Kinases
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JAK1 protein, human
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JAK2 protein, human
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JAK3 protein, human
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Janus Kinase 1
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Janus Kinase 2
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Janus Kinase 3