Clusterin: the missing link in the calcium-dependent resistance of cancer cells to apoptogenic stimuli.
The resistance of cancer cells to artificially induced apoptosis comprises a major pitfall in contemporary chemotherapy. In recent years, a wide range of molecular mechanisms was revealed that allow cancer cells to overcome apoptosis. In prostate, breast, and colorectal cancers, a protein named clusterin was identified with anti- or proapoptotic activity regulated by calcium homeostasis. Reports so far suggest "two faces" of clusterin activity: the calcium-dependent cellular retention of clusterin positively correlates with cell survival, whereas nuclear translocation of this protein promotes cell death in calcium-deprived cells. Better understanding of the proprieties of clusterin isoforms and the molecular mechanisms which regulate its activity provide the prospect of breaking down cancer cells' resistance to apoptosis. Thus one might expect such dual benefits as overcoming the "immune escape" of neoplastic cells and reducing the doses of cytostatic drugs, with a concomitant reduction in the side effects of chemotherapy.
Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw Agricultural University, Warsaw.
Beata
B
Pajak
Arkadiusz
A
Orzechowski
D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism; D051152:Clusterin / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism; D019139:Tumor Escape
D034961:Antigens, Nuclear; D000970:Antineoplastic Agents; D051152:Clusterin; D004268:DNA-Binding Proteins; D016328:NF-kappa B; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen