Depletion of the histone chaperone tNASP inhibits proliferation and induces apoptosis in prostate cancer PC-3 cells.
Depletion of the histone chaperone tNASP inhibits proliferation and induces apoptosis in prostate cancer PC-3 cells.
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DOI：
10.1186/1477-7827-9-50
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发表时间：
2011-04-16
期刊：
影响因子：
--
通讯作者：
O'Rand MG
中科院分区：
文献类型：
--
作者：
Alekseev OM;Richardson RT;Tsuruta JK;O'Rand MG
NASP (Nuclear Autoantigenic Sperm Protein) is a histone chaperone that is present in all dividing cells. NASP has two splice variants: tNASP and sNASP. Only cancer, germ, transformed, and embryonic cells have a high level of expression of the tNASP splice variant. We examined the consequences of tNASP depletion for prostate cancer PC-3 cells. tNASP was depleted from prostate cancer PC-3 cells, cervical cancer HeLa cells, and prostate epithelial PWR-1E cells using lentivirus expression of tNASP shRNA. Cell cycle changes were studied by proliferation assay with CFSE labeling and double thymidine synchronization. Gene expression profiles were detected using RT2Profiler PCR Array, Western and Northern blotting. PC-3 and HeLa cells showed inhibited proliferation, increased levels of cyclin-dependant kinase inhibitor p21 protein and apoptosis, whereas non-tumorigenic PWR-1E cells did not. All three cell types showed decreased levels of HSPA2. Supporting in vitro experiments demonstrated that tNASP, but not sNASP is required for activation of HSPA2. Our results demonstrate that PC-3 and HeLa cancer cells require tNASP to maintain high levels of HSPA2 activity and therefore viability, while PWR-1E cells are unaffected by tNASP depletion. These different cellular responses most likely arise from changes in the interaction between tNASP and HSPA2 and disturbed tNASP chaperoning of linker histones. This study has demonstrated that tNASP is critical for the survival of prostate cancer cells and suggests that targeting tNASP expression can lead to a new approach for prostate cancer treatment.
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影响因子：
82.9
作者：
Carbone, M;Rizzo, P;Pass, HI
通讯作者：
Pass, HI
DOI：
10.1530/ror.0.0040023
发表时间：
1999-01-01
期刊：
REVIEWS OF REPRODUCTION
影响因子：
--
作者：
Eddy, EM
通讯作者：
Eddy, EM
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
13.2
作者：
Jeruc, Jera;Vizjak, Alenka;Ferluga, Dusan
通讯作者：
Ferluga, Dusan
影响因子：
4.8
作者：
Alekseev, OM;Widgren, EE;O'Rand, MG
通讯作者：
O'Rand, MG