A truncated human Ah receptor suppresses growth of human cervical tumor xenografts by interfering with hypoxia signaling

Wang, Depeng; Faridi, Jesika S.; Li, Yanjie; Chan, William K.

doi:10.1016/j.febslet.2009.08.013

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Volume 583, Issue 18 , Pages 3039-3044, 17 September 2009

A truncated human Ah receptor suppresses growth of human cervical tumor xenografts by interfering with hypoxia signaling

Edited by Robert Barouki

Depeng Wang
- Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, United States
Jesika S. Faridi
- Department of Physiology and Pharmacology, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, United States
Yanjie Li
- Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, United States
William K. Chan
- Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, United States
- Corresponding author. Fax: +1 209 946 2160.

Received 3 August 2009; accepted 12 August 2009. published online 18 August 2009.

Abstract

We used a xenograft model to investigate whether the aryl hydrocarbon receptor deletion construct CΔ553 suppresses tumor growth. HeLa cells that were infected with CΔ553 expressing adenovirus (Ad553) formed very small tumors whereas the control adenovirus-infected cells formed large tumors at day 15. CΔ553 inhibited the formation of the HIF-1 DNA complex and suppressed the induction of the HIF-1α target proteins CAIX and GLUT1. The Ad553 tumors had less HIF-1 function since they showed reduced microvessel formation and lesser amounts of HIF-1α, Arnt, phospho-Akt, CAIX, and GLUT1. Proteasome-mediated Arnt degradation was enhanced in Ad553-infected HeLa cells and tumors.

Keywords: Arnt, HIF-1α, AhR, Xenograft tumor