Clusterin isoforms differentially affect growth and motility of prostate cells : possible implications in prostate tumorigenesis
Articolo
Data di Pubblicazione:
2007
Citazione:
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]
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]
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
R.M. Moretti, M. Montagnani Marelli, S. Mai, A. Cariboni, M. Scaltriti, S. Bettuzzi, P. Limonta
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