Maspin modulates prostate cancer cell apoptotic and angiogenic response to hypoxia via targeting AKT
Open Access
- 20 October 2008
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 27 (57), 7171-7179
- https://doi.org/10.1038/onc.2008.321
Abstract
Hypoxia has been previously linked to the development of both benign prostatic hyperplasia and prostate cancer. This study investigated the effect of maspin, an extracellular matrix (ECM) tumor suppressor, on the apoptotic response of prostate cancer cells to hypoxia. Gene expression profiling of human benign and malignant prostate epithelial cells after exposure to hypoxia or normoxia revealed dramatic changes in ECM regulators. Maspin was found to be overexpressed in response to hypoxia in prostate cancer cells, but not in benign prostate cells. To dissect the contribution of maspin to tumor cell responses within a hypoxic microenvironment, we used maspin-overexpressing DU-145 human prostate cancer cells. Exposure to hypoxic conditions (1% O2) led to a significant increase in apoptosis in the DU-145 maspin cells, compared to DU-145 neo-transfectants without a significant effect on cell migration. This enhanced sensitivity to hypoxia-induced apoptosis leads to a significant suppression of tumor growth and tumor vascularity in vivo by targeting Akt and focal adhesion kinase activation. Our findings implicate maspin in prostate cancer cell response to hypoxia via recruitment of intracellular signaling partners. This study may have significance in the identification of maspin-driven therapeutic targeting in advanced metastatic prostate cancer.Keywords
This publication has 32 references indexed in Scilit:
- Novel Quinazoline-Based Compounds Impair Prostate Tumorigenesis by Targeting Tumor VascularityCancer Research, 2007
- A hypoxia-independent up-regulation of hypoxia-inducible factor-1 by AKT contributes to angiogenesis in human gastric cancerCarcinogenesis: Integrative Cancer Research, 2007
- Loss of maspin expression contributes to a more invasive potential in malignant melanomaPigment Cell Research, 2007
- Anoikis and Survival Connections in the Tumor Microenvironment: Is There a Role in Prostate Cancer Metastasis?Cancer Research, 2005
- Hypoxia‐inducible factor 1α modulates adhesion, migration, and FAK phosphorylation in vascular smooth muscle cellsJournal of Cellular Biochemistry, 2005
- Maspin sensitizes prostate cancer cells to doxazosin-induced apoptosisOncogene, 2005
- In vitro study of HIF-1 activation and VEGF release by bFGF in the T47D breast cancer cell line under normoxic conditions: involvement of PI-3K/Akt and MEK1/ERK pathwaysThe Journal of Pathology, 2005
- Targeting HIF-1 for cancer therapyNature Reviews Cancer, 2003
- The biology of VEGF and its receptorsNature Medicine, 2003
- Recent advances in insulin gene therapy for type 1 diabetesTrends in Molecular Medicine, 2002