P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling

Kiyosumi Shibata, Hiroaki Kajiyama, Kazuhiko Ino, Akihiro Nawa, Seiji Nomura, Shigehiko Mizutani, Fumitaka Kikkawa

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Hyperglycemia or hyperinsulinemia contributes to poorer endometrial cancer survival. It was shown that P-LAP/IRAP translocates to the plasma membrane in response to insulin stimulation. Recently, we demonstrated that P-LAP/IRAP is associated with a poor prognosis in endometrial adenocarcinoma patients. The aim of this study was to examine whether the malignant potential of endometrial cancer enhanced by P-LAP/IRAP is due to increased glucose uptake via the P-LAP/ IRAP-mediated activation of insulin signaling. Methods: We transfected P-LAP/IRAP cDNA into A-MEC cells (endometrial adenocarcinoma cell line), and A-MEC-LAP cells expressed a remarkably high level of GLUT4 proteins. Results: 3H-2-deoxyglucose uptake which responds to insulin in A-MEC-LAP cells was significantly higher than that of A-MEC-pc cells. A-MEC-LAP cells exhibited a significant growth-stimulatory effect compared to A-MEC-pc cells. A-MEC-LAP cells expressed a remarkably high level of p85PI3K protein compared to A-MEC-pc cells, and showed a higher degree of AKT phosphorylation by insulin stimulation. Conclusion: In summary, P-LAP/IRAP was involved in the increasing malignant potential of endometrial cancer mediated by insulin. P-LAP/ IRAP was suggested to be a potential new target of molecular-targeted therapy for endometrial cancer.

Original languageEnglish
Article number15
JournalBMC Cancer
Volume7
DOIs
Publication statusPublished - 12-02-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

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