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Prostate Cancer Cell Growth (prostate + cancer_cell_growth)
Selected AbstractsTIP30 is associated with progression and metastasis of prostate cancerINTERNATIONAL JOURNAL OF CANCER, Issue 4 2008Hui Zhang Abstract Tat-interacting protein 30 (TIP30), a transcriptional repressor for ER,-mediated transcription, possesses several characteristics of a tumor suppressor in certain human and mouse cells. It is reported that deletion of TIP30 gene preferentially increases tumorigenesis in the female knockout mice. Here, we analyzed TIP30 gene expression in the databases of several DNA microarray studies of human prostate cancer and show that TIP30 is specifically overexpressed in metastatic prostate cancers. We demonstrate that TIP30 nuclear expression is associated with prostate cancer progression and metastasis by immunohistochemical analysis in primary and metastatic prostate cancers. Consistent with these data, we also show that knockdown of TIP30 expression, through use of a short hairpin RNA-expressing plasmid, suppresses the cellular growth of PC3 and LNCaP prostate cancer cells. Ectopic overexpression of TIP30 stimulates metastatic potential of prostate cancer cells in an in vitro invasion assay, whereas knockdown of TIP30 inhibits the prostate cancer cells invasion. Finally, we demonstrate that ectopic overexpression of TIP30 enhances androgen receptor mediated transcription, whereas knockdown of TIP30 results in a decreased transcription activity. These data provide evidence that TIP30 plays a role in prostate cancer progression and that TIP30 overexpression may promote prostate cancer cell growth and metastasis. © 2008 Wiley-Liss, Inc. [source] Emerging Evidence on the Role of Soy in Reducing Prostate Cancer RiskNUTRITION REVIEWS, Issue 4 2003Mark J. Messina PhD Soyfoods are a unique dietary source of isoflavones, which have both hormonal and non-hormonal effects relevant to prostate cancer prevention. In vitro, the main soybean isoflavone, genistein, inhibits prostate cancer cell growth; in animals, most but not all studies show isoflavone-rich soy protein and isolated isoflavones inhibit prostate tumor development. Currently, although only limited epidemiologic data indicate soy intake reduces prostate cancer risk, results from a pilot intervention trial suggest isoflavones may be beneficial to prostate cancer patients. For several reasons, men concerned about their prostate health may consider incorporating soy into their diet. [source] NF-,B2/p52 enhances androgen-independent growth of human LNCaP cells via protection from apoptotic cell death and cell cycle arrest induced by androgen-deprivationTHE PROSTATE, Issue 16 2008Nagalakshmi Nadiminty Abstract PURPOSE Androgen-deprivation therapy only causes a temporary regression of prostate cancer, as all tumors will eventually progress to refractory to hormonal therapy after 1,3 years of treatment. The underlying mechanisms of prostate cancer androgen refractory progression are incompletely understood. In this study, we employed in vitro as well as in vivo models to examine the role of NF-,B2/p52 in prostate cancer growth and androgen independent progression. EXPERIMENTAL DESIGN The effects of NF-,B2/p52 on cell growth, androgen responsiveness, cell cycle and apoptosis were examined in androgen sensitive LNCaP cells. The effect of NF-,B2/p52 on tumor growth was examined in intact and castrated male mice. RESULTS Overexpression of NF-,B2/p52 enhances androgen-sensitive LNCaP human prostate cancer cell growth and clonogenic ability in androgen-deprived condition in vitro. NF-,B2/p52 induced androgen-independent growth is through protecting LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. In addition, NF-,B2/p52 stimulates Cyclin D1 expression and knock down of Cyclin D1 expression by siRNA abolished NF-,B2/p52-induced cell growth in vitro. Adenoviral mediated NF-,B2/p52 expression in LNCaP cells enhances tumor growth in intact male nude mice and induces tumor growth in castrated male nude mice, suggesting that overexpression of NF-,B2/p52 induces androgen-independent growth of androgen-sensitive LNCaP cells. CONCLUSIONS Overexpression of NF-,B2/p52 protects androgen sensitive LNCaP cells from apoptotic cell death and cell cycle arrest induced by androgen-deprivation. NF-,B2/p52 activation induces androgen-independent growth in vitro and in vivo. Prostate © 2008 Wiley-Liss, Inc. [source] Experimental therapy of prostate cancer with novel natural product anti-cancer ginsenosides,THE PROSTATE, Issue 8 2008Wei Wang Abstract BACKGROUND Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25-hydroxyprotopanaxadiol (25-OH-PPD) and 25-hydroxyprotopanaxatriol (25-OH-PPT) from Panax ginseng and evaluated their anti-cancer activity in vitro. METHODS We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model. We also accomplished a preliminary determination of the mechanisms of action of the compounds. RESULTS 25-OH-PPD, but not 25-OH-PPT, inhibited prostate cancer cell growth and proliferation, induced apoptosis, and led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3 xenograft tumors, 25-OH-PPD inhibited tumor growth in a dose-dependent manner and could be safely combined with chemotherapeutic agents (taxotere and gemcitabine) and radiation therapy to improve the anti-tumor effects. Further, in both PC3 and LNCaP cell lines, 25-OH-PPD increased expression of p21, p27, and Bax, induced PARP cleavage and activated caspases. The compound also reduced expression of MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle arrest in G1 and the decrease in proliferation. Moreover, 25-OH-PPD demonstrated low toxicity to non-cancer cells and no observable host toxicity in animals either alone or in combination with conventional therapies. CONCLUSIONS The newly identified ginsenoside 25-OH-PPD may have potential as a novel prostate cancer therapeutic agent. Prostate 68:809,819, 2008. © 2008 Wiley-Liss, Inc. [source] Longitudinal analysis of androgen deprivation of prostate cancer cells identifies pathways to androgen independenceTHE PROSTATE, Issue 7 2008Jason M. D'Antonio Abstract BACKGROUND Following androgen ablation therapy, the majority of prostate cancer patients develop treatment resistance with a median time of 18,24 months to disease progression. METHODS To identify molecular targets that promote prostate cancer cell survival and contribute to androgen independence, we evaluated changes in LNCaP cell gene expression during 12 months of androgen deprivation. At time points reflecting critical growth and phenotypic changes, we performed Affymetrix expression array analysis to examine the effects of androgen deprivation during the acute response, during the period of apparent quiescence, and following the emergence of a highly proliferative, androgen-independent prostate cancer cell phenotype (LNCaP-AI). RESULTS We discovered alterations in gene expression for molecules associated with promoting prostate cancer cell growth and survival, and regulating cell cycle progression and apoptosis. Additionally, expression of AR co-regulators, adrenal androgen metabolizing enzymes, and markers of neuroendocrine disease were significantly altered. CONCLUSIONS These findings contribute greatly to our understanding of androgen-independent prostate cancer. The value of this longitudinal approach lies in the ability to examine gene expression changes throughout the adaptive response to androgen deprivation; it provides a more dynamic illustration of genes which contribute to disease progression in addition to specific genes which constitute an androgen-independent phenotype. Prostate 68: 698,714, 2008. © 2008 Wiley-Liss, Inc. [source] S179D prolactin sensitizes human prostate cancer cells such that physiological concentrations of 1, 25 dihydroxy vitamin D3 result in growth inhibition and cell deathTHE PROSTATE, Issue 14 2007Wei Wu Abstract BACKGROUND S179D Prolactin (PRL) is a molecular mimic of naturally phosphorylated human PRL which has been shown to inhibit the growth of human prostate cancer cells both in vitro and when grown as tumors in nude mice. METHODS In the current study, we have investigated the potential interplay between S179D PRL and 1,25 dihydroxy vitamin D3 (1,25D) in the inhibition of prostate cancer cell growth by incubating cells under circumstances where each hormone alone has no effect. RESULTS Incubation of DU145 or PC3 cells in 100 pM 1,25D or 10 nM S179D PRL for 3 days showed no effect of each alone on expression of the vitamin D receptor (VDR), or the cell cycle regulatory protein p21, or on cell number. Incubation in both together increased expression of the VDR and p21 two to threefold. This co-operative effect was reproduced when activation of the p21 promoter was analyzed using a p21-luciferase (p21-luc) construct. Elimination of the VDR response element from p21-luc eliminated response to the hormone combination, showing that the effect on p21 was through the VDR. Most importantly, S179D PRL sensitized the cells to 1,25D such that there was a concentration-related reduction in cell number versus controls between 40 and 160 pM. At least part of this effect was via the induction of cell death. CONCLUSIONS These results suggest that combined anti-tumor therapy may be very efficacious and that the dose of 1,25D required may be below the range that results in hypercalcemia. Prostate 67: 1498,1506, 2007. © 2007 Wiley-Liss, Inc. [source] Regulation of prostate cancer cell growth and PSA expression by angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma ligand like actionTHE PROSTATE, Issue 9 2007Hitoshi Ishiguro Abstract BACKGROUND We previously reported that angiotensin II (AII) activated the proliferation of prostate cancer cells, and its antagonist, an AII receptor type 1 (AT1R) blocker (ARB), inhibited the proliferation of prostate cancer in vitro and in vivo. In the present study, we investigated whether telmisartan, an ARB, has a unique feature as a peroxisome proliferator-activated receptor , (PPAR,) ligand, and its suppressive potential on prostate cancer cells. METHODS Cell count or MTT assay were carried out for growth suppression of prostate cancer cells. Phosphorylation of mitogen-activated protein kinase (MAPK), specific expression of prostate specific antigen (PSA) and AT1R were investigated by western blot. To confirm the PPAR, activity of ARBs, luciferase assay using PSA promoter and PPAR, response elements (PPRE) plasmids was performed. RESULTS The results showed that cell proliferation and signal transduction were inhibited by telmisartan treatment. Also, inhibition of PSA expression by telmisartan was confirmed by western blot and luciferase assay, indicating that an ARB acted in a similar way such as an anti-androgenic agent in prostate cancer cells. CONCLUSION The present study showed ARBs, especially those possessing a PPAR, ligand-like structure, have a potential antagonistic effect on androgen-dependent and -independent prostate cancer. Prostate 67: 924,932, 2007. © 2007 Wiley-Liss, Inc. [source] C/EBP, is a downstream mediator of IL-6 induced growth inhibition of prostate cancer cellsTHE PROSTATE, Issue 2 2005Daniel C. Sanford Abstract BACKGROUND Although a number of reports have investigated the effects of IL-6 family cytokines on prostate cell growth, there is limited information available identifying IL-6 inducible downstream effector genes and their function in growth control. Previous studies have demonstrated that IL-6 treatment results in the activation of signal transducer and activator of transcription3 (STAT3) in prostate cancer cells. The goal of this study was to investigate the influence of IL-6 treatment and activation of the Jak/STAT signal transduction pathway on C/EBP, gene expression and growth inhibition of human prostate cancer cells. METHODS Expression of C/EBP, and STAT3 activation were assayed using Northern and Western blotting techniques. Proliferation was assessed by [3H] thymidine incorporation, flow cytometry, and colony formation analyses. The analysis of the transcriptional regulation of C/EBP, was performed using luciferase-reporter constructs. RESULTS In this report, we demonstrate that IL-6 treatment induces STAT3 activation (pSTAT3), pSTAT3 binds to the human C/EBP, gene promoter and induces its expression. We also demonstrate that C/EBP, over-expression is capable of suppressing prostate cancer cell growth. CONCLUSIONS These results demonstrate that C/EBP, gene expression is increased in IL-6 treated LNCaP cells. Increased C/EBP, gene expression plays an important role in IL-6/STAT3 mediated growth arrest of LNCaP prostate cancer cells. Ongoing studies are investigating the mechanism by which C/EBP, controls prostate cancer cell growth and the potential role of C/EBP, in the survival and chemo resistance of prostate cancer metastasis. © 2004 Wiley-Liss, Inc. [source] Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancerCANCER SCIENCE, Issue 5 2009Kenji Tamura Prostate cancer is usually androgen-dependent and responds well to androgen ablation therapy based on castration. However, at a certain stage some prostate cancers eventually acquire a castration-resistant phenotype where they progress aggressively and show very poor response to any anticancer therapies. To characterize the molecular features of these clinical castration-resistant prostate cancers, we previously analyzed gene expression profiles by genome-wide cDNA microarrays combined with microdissection and found dozens of trans -activated genes in clinical castration-resistant prostate cancers. Among them, we report the identification of a new biomarker, stanniocalcin 2, as an overexpressed gene in castration-resistant prostate cancer cells. Real-time polymerase chain reaction and immunohistochemical analysis confirmed overexpression of stanniocalcin 2, a 302-amino-acid glycoprotein hormone, specifically in castration-resistant prostate cancer cells and aggressive castration-naïve prostate cancers with high Gleason scores (8,10). The gene was not expressed in normal prostate, nor in most indolent castration-naïve prostate cancers. Knockdown of stanniocalcin 2 expression by short interfering RNA in a prostate cancer cell line resulted in drastic attenuation of prostate cancer cell growth. Concordantly, stanniocalcin 2 overexpression in a prostate cancer cell line promoted prostate cancer cell growth, indicating its oncogenic property. These findings suggest that stanniocalcin 2 could be involved in aggressive phenotyping of prostate cancers, including castration-resistant prostate cancers, and that it should be a potential molecular target for development of new therapeutics and a diagnostic biomarker for aggressive prostate cancers. (Cancer Sci 2009; 100: 914,919) [source] | ||||||||||