Beyond The Abstract Clusterin Isoforms Differentially Affect Growth And Motility Of Prostate Cells: Possible Implications In Prostate Tumorigenesis
The finding that a nuclear form of CLU (nCLU) inhibits growth and migration of prostate cancer cells, inducing a dramatic remodelling/dismantling of the actin cytoskeleton by binding α-actinin (a key protein for the regulation of actin cytoskeleton) is of high relevance, shedding new light on the field and revealing that nCLU is a potent tumor-suppressor factor capable to inhibit metastatic diffusion of prostate cancer cells. In addition, CLU was previously found down-regulated in prostate cancer 1 and capable to induce cell death of immortalized and metastatic prostate cancer cells 2-4. Thus, indeed CLU gene expression plays a crucial role in prostate tumorigenesis, but quite differently from what was previously believed.
As a matter of fact, a clinical trial in which antisense oligonicleotides against CLU are given to prostate cancer patients has started 5. This is based on the idea that CLU expression would promote tumorigenesis. These novel data lead to the important conclusion that great caution has to be exerted before attempting clinical trials in which depletion of CLU is induced by antisense strategy to prostate cancer patients. This approach may result in no or unpredictable/undesirable effects, because based on the wrong rationale. At the time when this trial was launched, these information were not available: thus more caution should have been used before starting a clinical trial investigation involving CLU as main target in prostate cancer cells.
1. References: M. Scaltriti, M. Brausi, A. Amorosi, A. Caporali, D. D'Arca, S. Astancolle, A. Corti and S. Bettuzzi, Clusterin (SGP-2, ApoJ) expression is down-regulated in low and high grade human prostate cancer, Int. J. Cancer 108 (2004) 23 30
2. S. Bettuzzi, F. Scorcioni, S. Astancolle, P. Davalli, M. Scaltriti, A. Corti, Clusterin (SGP-2) transient overexpression decreases proliferation rate of SV40-immortalised human prostate epithelial cells by slowing down cell cycle progression, Oncogene 21 (2002) 4328 4334
3. A.E. Caccamo, M. Scaltriti, A. Caporali, D. D'Arca, A. Corti, D. Corvetta, A. Sala, S. Bettuzzi, Ca2+ depletion caused nuclear translocation of a 45kda death-isoform of clusterin and anoikis induction in prostate cells, Cell Death Diff. 12 (2005) 101 104
4. M. Scaltriti, A. Santamaria, R. Paciucci, S. Bettuzzi, Intracellular clusterin induces G2/M-phase arrest and cell death in PC-3 prostate cancer cells, Cancer Res. 64 (2004) 6174 6182
5. Use of antisense oligonucleotides targeting the cytoprotective gene, clusterin, to enhance androgen- and chemo-sensitivity in prostate cancer, World J Urol 23 (2005) 38 46
Written by
Saverio Bettuzzi, MD, as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
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Dincolo de Clusterin Rezumat izoformele diferenþia Affect creºtere economicã ºi motilitãþii de prostatã Cells: posibilele implicaþii În Tumorigenesis de prostatã - Beyond The Abstract Clusterin Isoforms Differentially Affect Growth And Motility Of Prostate Cells: Possible Implications In Prostate Tumorigenesis - articole medicale engleza - startsanatate