Abstract
The biological functions of clusterin (CLU, also known as ApoJ, SGP2, TRPM-2, CLI) have been puzzling the researchers since its first discovery in the early 80's. We know that CLU is a single 9-exons gene expressing three protein forms with different sub-cellular localisations and diverse biological functions. Despite the many reports from many research teams on CLU action and its relation to tumourigenesis, contradictions in the data and alternative hypothesis still exist. Understanding the role of CLU in tumourigenesis is complicated not only by the existence of different protein forms but also by the changes of tumours over time and the selection pressures imposed by treatments such as hormone ablation or chemotherapy. This review focuses on recent discoveries concerning the role of CLU in prostate and breast cancer onset and progression. Although CLU acts primarily as a tumour suppressor in the early stages of carcinogenesis, consistent with its role in the involution of the prostate following castration, late stage cancer may overexpress CLU following chemotherapeutic drugs or hormonal ablation therapy. High expression of secreted or cytoplasmic CLU may represent a pro-survival stimulus because it confers increased resistance to killing by anti-cancer drugs or enhances tumour cell survival in specific niches.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adenocarcinoma / etiology*
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenocarcinoma / prevention & control
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Adenocarcinoma / therapy
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Animals
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / therapeutic use
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Antineoplastic Agents, Hormonal / therapeutic use
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Apoptosis / genetics
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Apoptosis / physiology
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Breast Neoplasms / etiology*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Catechin / therapeutic use
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Cell Transformation, Neoplastic
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Clusterin / genetics
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Clusterin / metabolism
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Clusterin / physiology*
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Drug Resistance, Neoplasm / physiology
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Epigenesis, Genetic
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Male
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Mice
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Neoplasm Proteins / physiology*
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Neoplasms, Hormone-Dependent / drug therapy
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Neoplasms, Hormone-Dependent / metabolism
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Neoplasms, Hormone-Dependent / pathology
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Neoplasms, Hormone-Dependent / surgery
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Oncogenes
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Orchiectomy
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Prostatic Neoplasms / etiology*
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Prostatic Neoplasms / genetics
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology
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Prostatic Neoplasms / prevention & control
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Prostatic Neoplasms / therapy
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Protein Isoforms / physiology
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Tumor Suppressor Proteins / physiology
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Antineoplastic Agents, Hormonal
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CLU protein, human
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Clusterin
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Neoplasm Proteins
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Protein Isoforms
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Tumor Suppressor Proteins
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Catechin