Prostate secretory protein (PSP94) suppresses the growth of androgen-independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis

Garde, Seema V.; Basrur, Vathsala S.; Li, Li; Finkelman, Malcolm; Krishan, Awtar; Wellham, Larry L.; Ben‐Josef, Edgar; Haddad, Maher M.; Taylor, John D.; Porter, Arthur T.; Tang, Dean G.

doi:10.1002/(sici)1097-0045(19990201)38:2<118::aid-pros5>3.0.co;2-g

Cited by 69 publications

(60 citation statements)

References 13 publications

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“…9 The ectopic expression of PSP94 was associated with a decreased colony formation of the PCa cell lines LNCaP and WPE1-NB26, but not of the prostate carcinoma PC-3 cell line. The absence of an effect on PC-3 cells is at variance with another report 14 and the generally established function of PSP94 as a tumor suppressor. However, as suggested by the authors, such differences can be due to the distinct modes of PSP94 delivery, i.e., by the transfection of the PSP94-expressing construct 6 or the addition of PSP94 protein to the culture medium.…”

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confidence: 77%

“…However, as suggested by the authors, such differences can be due to the distinct modes of PSP94 delivery, i.e., by the transfection of the PSP94-expressing construct 6 or the addition of PSP94 protein to the culture medium. 14 The ectopic expression of CRISP-3 caused a growth inhibition of PC-3 and WPE1-NB26 cells, but not of LNCaP cells, which represents a cell line specificity that is different from that of PSP94. Moreover, growth inhibition of PC-3 cells by CRISP-3 was not affected by the stable expression of PSP94, which is further evidence that this effect of CRISP-3 is not mediated by PSP94.…”

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confidence: 98%

“…2 It also reduces the proliferation of rat cancer cell lines, human androgen-independent prostate cell lines and xenografted tumors by inducing apoptosis. 14,15 The current view is that the biological effects of PSP94 are largely mediated by protein-protein interactions. Indeed, PSP94 attaches to cell membranes and forms homo-and heterodimers ( Figure 1b).…”

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Growth inhibition properties of the putative prostate cancer biomarkers PSP94 and CRISP-3

Eynde¹,

Litovkin²

2010

Asian J Androl

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confidence: 98%

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Growth inhibition properties of the putative prostate cancer biomarkers PSP94 and CRISP-3

Eynde¹,

Litovkin²

2010

Asian J Androl

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“…The tumor suppressor PSP94, also known as b-microseminoprotein or prostatic inhibin, is a small (10.7 kDa), non-glycosylated and cysteine-rich protein that is abundantly secreted by the prostate gland and is found in both seminal fluid and blood (Garde et al, 1999;Shukeir et al, 2003;Annahi et al, 2005;Lamy et al, 2006). It is not known how the expression of the PSP94-encoding MSMB gene is regulated.…”

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confidence: 99%

“…However, it is well established that the expression of PSP94 progressively decreases during the development of prostate cancer from an early, low-invasive, androgen-dependent state to a late, highly invasive, androgen-refractory state (LaTulippe et al, 2002;Vanaja et al, 2003;Stanbrough et al, 2006). The gradual loss of PSP94 is likely to contribute to the development of prostate cancer because PSP94 impedes prostate cancer growth and metastasis (Garde et al, 1999;Shukeir et al, 2003Shukeir et al, , 2004. The molecular basis for the tumor-suppressor function of PSP94 is complex as this protein has been found to promote tumor cell apoptosis (Garde et al, 1999), to inhibit the secretion of a matrix metalloproteinase that is implicated in tumor metastasis (Annahi et al, 2005), and to decrease tumor-associated, vascular endothelial growth factor (VEGF)-mediated vascularization (Lamy et al, 2006).…”

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confidence: 99%

The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

et al. 2007

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BelgiumPSP94, for prostatic secretory protein of 94 amino acids, is secreted by the prostate gland and functions as a suppressor of tumor growth and metastasis. The expression of PSP94 is lost in advanced, hormone-refractory prostate cancer and this correlates with an increased expression of the Polycomb protein EZH2 (enhancer of zeste homolog 2), which represses transcription via trimethylation of histone H3 on Lys27 (H3K27). We show here that these events are causally related and that the MSMB gene, which encodes PSP94, is trimethylated on H3K27 in androgen-refractory, but not in androgensensitive prostate cancer cells. Chromatin immunoprecipitation experiments confirmed an association of EZH2 with the MSMB gene. The RNAi-mediated knockdown of EZH2 resulted in a loss of H3K27 trimethylation and an increased expression of the MSMB gene. Conversely, the overexpression of EZH2 was associated with a decreased expression of the MSMB gene. We also demonstrate that MSMB is additionally repressed in androgen-refractory prostate cancer cells by the hypoacetylation of histone H3K9 and the hypermethylation of a CpG island in the promoter region. Our data disclose a hitherto unexplored link between the putative oncogene EZH2 and the tumor suppressor PSP94, and show that MSMB is silenced by EZH2 in advanced prostate cancer cells.

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Identification of a specifically expressed modified form of novel PSP‐94 protein in the secretion of benign prostatic hyperplasia

Wang

Ling

et al. 2003

Electrophoresis

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Using two-dimensional gel electrophoresis, we investigated the profile of prostatic secretory proteins in human expressed prostatic secretion (EPS) from benign prostate hyperplasia (BPH) patients and compared the patterns with normal controls. We identified three specifically expressed proteins, including prostate secretory protein 61 (PSP61), in EPS from benign BPH patients but absent in normal controls. In addition, we found that PSP61 was a modified isoform of the well-documented PSP-94, which had a perfect matching (100% homology) to the first 61 amino acids of the PSP-94 protein but with a deleted C-terminus. This shortened PSP61 was not due to alternative splicing of the PSP-94 gene at transcription level. Our results provide first evidence on the possibility of using PSP61 as a specific biological marker for diagnosis of BPH.

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Prostate secretory protein (PSP94) suppresses the growth of androgen-independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis

Cited by 69 publications

References 13 publications

Growth inhibition properties of the putative prostate cancer biomarkers PSP94 and CRISP-3

Growth inhibition properties of the putative prostate cancer biomarkers PSP94 and CRISP-3

The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

Identification of a specifically expressed modified form of novel PSP‐94 protein in the secretion of benign prostatic hyperplasia

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