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

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.

• Authors: Kiyosumi Shibata, Hiroaki Kajiyama, Kazuhiko Ino, Akihiro Nawa, Seiji Nomura, Shigehiko Mizutani, Fumitaka Kikkawa
• Journal: BMC cancer (BMC Cancer) Vol. 7 Pg. 15 (Jan 19 2007) ISSN: 1471-2407 [Electronic] England
• PMID: 17233921 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucose Transporter Type 4
• Receptor, Insulin
• Cystinyl Aminopeptidase
• leucyl-cystinyl aminopeptidase
• Glucose

Topics

• Analysis of Variance
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation
• Cystinyl Aminopeptidase (metabolism)
• Endometrial Neoplasms (metabolism, pathology)
• Female
• Glucose (pharmacokinetics)
• Glucose Transporter Type 4 (metabolism)
• Humans
• Immunohistochemistry
• In Vitro Techniques
• Receptor, Insulin (metabolism, physiology)
• Signal Transduction (drug effects)
• Transfection