RLIP76: a target for kidney cancer therapy

Cancer Res. 2009 May 15;69(10):4244-51. doi: 10.1158/0008-5472.CAN-08-3521. Epub 2009 May 5.

Abstract

RLIP76 is a multifunctional transporter protein that serves as an energy-dependent efflux mechanism for endogenously generated toxic metabolites as well as exogenous toxins, including chemotherapy drugs. Our recent studies in cultured cells, syngeneic animal tumor model, and in xenograft model have shown that RLIP76 serves a major cancer-specific antiapoptotic role in a wide variety of histologic types of cancer, including leukemia, melanoma, colon, lung, prostate, and ovarian cancer. Results of present studies in cell culture and xenograft model of Caki-2 cells show that RLIP76 is an important anticancer for kidney cancer because inhibition of RLIP76 function by antibody or its depletion by small interfering RNA or antisense DNA caused marked and sustained regression of established human kidney xenografts of Caki-2 cells in nude mouse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / immunology
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Annexin A5 / physiology
  • Apoptosis
  • Cell Line, Tumor
  • Cell Survival
  • DNA, Antisense / genetics
  • GTPase-Activating Proteins / antagonists & inhibitors
  • GTPase-Activating Proteins / immunology
  • GTPase-Activating Proteins / metabolism*
  • Glomerular Mesangium / metabolism
  • Humans
  • In Situ Nick-End Labeling
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Liposomes
  • Mice
  • Mice, Nude
  • RNA, Small Interfering / genetics
  • Transplantation, Heterologous

Substances

  • ATP-Binding Cassette Transporters
  • Annexin A5
  • DNA, Antisense
  • GTPase-Activating Proteins
  • Liposomes
  • RALBP1 protein, human
  • RNA, Small Interfering