Abstract
Methylation of CpG islands of tumor suppressor genes, growth factors, and hormone receptors among other genes causes epigenetic changes in chromatin structure without altering DNA sequence to regulate transcription of these genes. This epigenetic regulation of gene expression plays an important role in the process of tumor invasion, growth and metastasis in malignancies. In hormone dependent malignancies such as breast and prostate cancer, sex steroids play an important role in the process of tumor initiation and progression. These malignancies are often initiated as a less aggressive hormone-responsive type that gradually progresses to become highly invasive and hormone-insensitive. At the early stages, cells lose a functional hormone receptor due to mutations, blockage of signaling pathway or hormone receptor gene silencing. This transition of cancer cells causes them to become refractory to the standard hormone therapies. In later stages, important factors like growth factors, cytokines and proteases promote tumor growth, invasion and metastases. The most commonly implicated protease in these processes is urokinase type plasminogen activator (uPA), which is known to be expressed in a number of malignancies including breast and prostate cancer and is directly associated with the higher invasive and metastatic potential of malignancies. In this chapter, we will review DNA methylation as the underlying molecular mechanism regulating uPA gene expression and its potential diagnostic, prognostic and therapeutic implication.
Keywords: urokinase, dna methylation, metastasis, prognostic, therapeutic, breast cancer, prostate cancer
Current Cancer Drug Targets
Title: Hypomethylation of Urokinase (uPA) Promoter in Breast and Prostate Cancer: Prognostic and Therapeutic Implications
Volume: 5 Issue: 7
Author(s): Pouya Pakneshan, Moshe Szyf and Shafaat A. Rabbani
Affiliation:
Keywords: urokinase, dna methylation, metastasis, prognostic, therapeutic, breast cancer, prostate cancer
Abstract: Methylation of CpG islands of tumor suppressor genes, growth factors, and hormone receptors among other genes causes epigenetic changes in chromatin structure without altering DNA sequence to regulate transcription of these genes. This epigenetic regulation of gene expression plays an important role in the process of tumor invasion, growth and metastasis in malignancies. In hormone dependent malignancies such as breast and prostate cancer, sex steroids play an important role in the process of tumor initiation and progression. These malignancies are often initiated as a less aggressive hormone-responsive type that gradually progresses to become highly invasive and hormone-insensitive. At the early stages, cells lose a functional hormone receptor due to mutations, blockage of signaling pathway or hormone receptor gene silencing. This transition of cancer cells causes them to become refractory to the standard hormone therapies. In later stages, important factors like growth factors, cytokines and proteases promote tumor growth, invasion and metastases. The most commonly implicated protease in these processes is urokinase type plasminogen activator (uPA), which is known to be expressed in a number of malignancies including breast and prostate cancer and is directly associated with the higher invasive and metastatic potential of malignancies. In this chapter, we will review DNA methylation as the underlying molecular mechanism regulating uPA gene expression and its potential diagnostic, prognostic and therapeutic implication.
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Cite this article as:
Pakneshan Pouya, Szyf Moshe and Rabbani A. Shafaat, Hypomethylation of Urokinase (uPA) Promoter in Breast and Prostate Cancer: Prognostic and Therapeutic Implications, Current Cancer Drug Targets 2005; 5 (7) . https://dx.doi.org/10.2174/156800905774574011
DOI https://dx.doi.org/10.2174/156800905774574011 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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