Leptin receptor expression and its association with PI3K/AKT signaling pathway in diffuse large B-cell lymphoma

Leuk Lymphoma. 2010 Jul;51(7):1305-14. doi: 10.3109/10428191003802365.

Abstract

We investigated the role of the leptin receptor (Ob-R) and its relationship with PI3K/AKT activation in diffuse large B-cell lymphoma (DLBCL) clinical samples followed by in vitro studies using a panel of CRC cell lines. Leptin exerts its physiological action through its receptor Ob-R. Overexpression of Ob-R has been implicated in the pathogenesis of a variety of malignancies; however, its role in DLBCL has not been investigated. Using immunohistochemistry on a large cohort of DLBCL samples in a tissue microarray format, Ob-R immunostaining was detected in 86/216 (39.8%). Ob-R overexpression was associated with the catalytic subunit p110 of PI3K (p = 0.0283), activated AKT (p = 0.0003), and antiapoptotic marker XIAP (p = 0.0008) expression. In in vitro analysis using DLBCL cell lines, our data showed that leptin stimulated cell proliferation and inhibited apoptosis via activation of the PI3K/AKT signaling pathway. Pretreatment of DLBCL cells with Ob-R specific small interference RNA or inactivation of PI3K/AKT activity by LY294002 abolished these responses. Altogether, these data suggest that leptin plays a critical role in DLBCL pathogesis through the P13K/AKT pathway via Ob-R.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation*
  • Female
  • Humans
  • Immunoblotting
  • Immunoenzyme Techniques
  • Leptin / metabolism
  • Lymphoma, Large B-Cell, Diffuse / metabolism*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Small Interfering / pharmacology
  • Receptors, Leptin / antagonists & inhibitors
  • Receptors, Leptin / genetics
  • Receptors, Leptin / metabolism*
  • Signal Transduction

Substances

  • Leptin
  • RNA, Small Interfering
  • Receptors, Leptin
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt