Human ovarian-carcinoma cell lines express IL-4 and IL-13 receptors: comparison between IL-4- and IL-13-induced signal transduction

Int J Cancer. 1997 Jan 17;70(2):230-40. doi: 10.1002/(sici)1097-0215(19970117)70:2<230::aid-ijc15>3.0.co;2-m.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Antigens, CD / biosynthesis*
  • Antigens, CD / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Insulin Receptor Substrate Proteins
  • Interleukin-13 / pharmacology*
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-4 / pharmacology*
  • Intracellular Signaling Peptides and Proteins
  • Janus Kinase 1
  • Janus Kinase 2
  • Janus Kinase 3
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational / drug effects*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins*
  • Receptors, Interleukin / biosynthesis*
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4
  • STAT6 Transcription Factor
  • Signal Transduction / drug effects*
  • Teratocarcinoma / genetics
  • Teratocarcinoma / metabolism
  • Teratocarcinoma / pathology*
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured / drug effects

Substances

  • Antigens, CD
  • IL13RA1 protein, human
  • IRS1 protein, human
  • IRS2 protein, human
  • Insulin Receptor Substrate Proteins
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Receptors, Interleukin
  • Receptors, Interleukin-13
  • Receptors, Interleukin-4
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Trans-Activators
  • Transcription Factors
  • Interleukin-4
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • JAK2 protein, human
  • JAK3 protein, human
  • Janus Kinase 1
  • Janus Kinase 2
  • Janus Kinase 3