PTEN Up-Regulates the Tumor Metastasis Suppressor Gene Drg-1 in Prostate and Breast Cancer
| Autor: | David Piquemal, Ken Saito, Sucharita Bandyopadhyay, Sudha K. Pai, Jodi I. Huggenvik, Shigeru Hirota, Ying Wang, Misako Watabe, Thérèse Commes, Yukio Takano, Kunio Miura, Kounosuke Watabe, Sadahiro Hosobe, Taisei Tsukada, Steven S. Gross |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Cancer Research Tumor suppressor gene Breast Neoplasms Cell Cycle Proteins Metastasis Prostate cancer Cell Line Tumor medicine Humans Tensin PTEN Genes Tumor Suppressor Metastasis suppressor Regulation of gene expression biology Tumor Suppressor Proteins Intracellular Signaling Peptides and Proteins PTEN Phosphohydrolase Prostatic Neoplasms medicine.disease Phosphoric Monoester Hydrolases Up-Regulation Gene Expression Regulation Neoplastic Survival Rate Metastasis Suppressor Gene Oncology Cancer research biology.protein Female |
| Zdroj: | Cancer Research. 64:7655-7660 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | PTEN (phosphatase and tensin homologue deleted on chromosome 10) has been shown to be inactivated in a wide variety of cancers, and the role of this gene as a tumor suppressor has been well established. On the other hand, results of recent animal studies as well as clinical evidence indicate that PTEN is also involved in tumor metastasis suppression. Although PTEN is known to play a key role in controlling cell growth and apoptosis, how PTEN exerts the metastasis suppressor function remains largely unknown. Recently, a microarray analysis identified the Drg-1 gene (differentiation related gene 1) as one of the potential targets of PTEN. The Drg-1 gene has been shown to suppress tumor metastasis in animal models of prostate and colon cancer, and the expression of this gene is significantly reduced with advancement of prostate and breast cancers in clinical setting. In this study, we explored the possibility that PTEN controls tumor metastasis by regulating the expression of the Drg-1 gene. Our results indicate that overexpression of PTEN significantly augments the endogenous expression of Drg-1 protein, whereas inhibition of PTEN by small interfering RNA decreases Drg-1 in a dose- and time-dependent manner. We also found that the control of the Drg-1 gene by PTEN seems to be at the transcriptional level, and that a phospho-Akt inhibitor restores the Drg-1 expression, indicating that PTEN controls Drg-1 by an Akt-dependent pathway. Consistent with these results, our immunohistochemical analysis revealed that PTEN expression correlates significantly with Drg-1 in both prostate and breast cancer cases. Furthermore, combination of the two markers, PTEN and Drg-1, emerged as a significantly better predictor of prostate and breast cancer patient survival than either marker alone. |
| Databáze: | OpenAIRE |
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