IL-2 enhances cervical cancer cells proliferation and JAK3/STAT5 phosphorylation at low doses, while at high doses IL-2 has opposite effects

Cancer Invest. 2014 May;32(4):115-25. doi: 10.3109/07357907.2014.883526. Epub 2014 Feb 18.

Abstract

The IL-2R signaling is critical for normal lymphocyte proliferation. However, the role of the IL-2 signaling in cervical cancer is not yet fully understood. We show that in IL-2R-expressing cervical cancer cells, JAK1 molecules are not phosphorylated. At low doses of IL-2, the constitutive phosphorylation of JAK3 and STAT5 increases in the tumor cells and decreases in lymphocytes, whereas the opposite occurs at high doses of IL-2. Using AG-490, the activation of JAK3 and the proliferation of cervical cancer cells were inhibited. We describe differences in the response of molecules downstream the IL-2R in lymphocytes and tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Interleukin-2 / pharmacology*
  • Janus Kinase 1 / metabolism
  • Janus Kinase 3 / metabolism*
  • Lymphocytes / drug effects
  • Lymphocytes / enzymology
  • Lymphocytes / pathology
  • Phosphorylation
  • Receptors, Interleukin-2 / drug effects
  • Receptors, Interleukin-2 / metabolism
  • Recombinant Proteins / pharmacology
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • IL2 protein, human
  • Interleukin-2
  • Receptors, Interleukin-2
  • Recombinant Proteins
  • STAT5 Transcription Factor
  • JAK1 protein, human
  • JAK3 protein, human
  • Janus Kinase 1
  • Janus Kinase 3