Abstract Besides a fully processed, secreted form of clusterin (sCLU), an alternative proapoptotic form of the protein targeting the nucleus (nCLU) was recently described. The possible differential roles played by the two clusterin forms in growth and motility of nonmalignant and malignant prostate cells are investigated here. sCLU or nCLU was transiently transfected in both androgen-independent prostate cancer cells (PC3 and DU 145) and immortalized prostate epithelial cells (PNT1A, a nontumoral control). Then, cell growth, motility, and cytoskeleton organization were studied. We found that (a) in PNT1A cells, both sCLU and nCLU significantly decreased cell proliferation and motility; (b) in PC3 and DU 145 cancer cells, only nCLU inhibited cell growth and migration, with sCLU being ineffective; and (c) the antimotility effect of nCLU was accompanied by a dramatic dismantling of the actin cytoskeleton. Moreover, transfection with ‘‘full-length’’ CLU cDNA produced both sCLU and nCLU in nonmalignant PNT1A cells, whereas only sCLU was found in cancer cells. Thus, CLU gene expression might play a crucial role in prostate tumorigenesis by exerting differential biological effects on normal versus tumor cells through differential processing of CLU isoforms in the two cell systems. We also found that nCLU binds to A-actinin, a key protein for the regulation of actin cytoskeleton, and that nCLU and A-actinin colocalize in the cytoplasm. Thus, the antimotility activity of nCLU and its ability to cause dismantling of the actin cytoskeleton seem to be mediated by its binding to A-actinin. [Cancer Res 2007; 67(21):10325–33]

Clusterin isoforms differentially affect growth and motility of prostate cells : possible implications in prostate tumorigenesis / R.M. Moretti, M. Montagnani Marelli, S. Mai, A. Cariboni, M. Scaltriti, S. Bettuzzi, P. Limonta. - In: CANCER RESEARCH. - ISSN 0008-5472. - 67:21(2007 Nov 01), pp. 10325-10333. [10.1158/0008-5472.CAN-07-0516]

Clusterin isoforms differentially affect growth and motility of prostate cells : possible implications in prostate tumorigenesis

R.M. Moretti
Primo
;
M. Montagnani Marelli
Secondo
;
S. Mai;A. Cariboni;P. Limonta
Ultimo
2007-11-01

Abstract

Abstract Besides a fully processed, secreted form of clusterin (sCLU), an alternative proapoptotic form of the protein targeting the nucleus (nCLU) was recently described. The possible differential roles played by the two clusterin forms in growth and motility of nonmalignant and malignant prostate cells are investigated here. sCLU or nCLU was transiently transfected in both androgen-independent prostate cancer cells (PC3 and DU 145) and immortalized prostate epithelial cells (PNT1A, a nontumoral control). Then, cell growth, motility, and cytoskeleton organization were studied. We found that (a) in PNT1A cells, both sCLU and nCLU significantly decreased cell proliferation and motility; (b) in PC3 and DU 145 cancer cells, only nCLU inhibited cell growth and migration, with sCLU being ineffective; and (c) the antimotility effect of nCLU was accompanied by a dramatic dismantling of the actin cytoskeleton. Moreover, transfection with ‘‘full-length’’ CLU cDNA produced both sCLU and nCLU in nonmalignant PNT1A cells, whereas only sCLU was found in cancer cells. Thus, CLU gene expression might play a crucial role in prostate tumorigenesis by exerting differential biological effects on normal versus tumor cells through differential processing of CLU isoforms in the two cell systems. We also found that nCLU binds to A-actinin, a key protein for the regulation of actin cytoskeleton, and that nCLU and A-actinin colocalize in the cytoplasm. Thus, the antimotility activity of nCLU and its ability to cause dismantling of the actin cytoskeleton seem to be mediated by its binding to A-actinin. [Cancer Res 2007; 67(21):10325–33]
Settore BIO/09 - Fisiologia
Settore BIO/13 - Biologia Applicata
Article (author)
File in questo prodotto:
File Dimensione Formato  
10325.full.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 532.64 kB
Formato Adobe PDF
532.64 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/35073
Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 53
  • ???jsp.display-item.citation.isi??? 53
social impact