RNA Interference-Directed Knockdown of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Inhibits Prostate Cancer Cell Invasion, Survival, and Tumorigenicity In Vivo

Pulukuri, Sai Murali Krishna; Gondi, Christopher S.; Lakka, Sajani S.; Jutla, Aman; Estes, Norman C.; Gujrati, Meena; Rao, Jasti S.

doi:10.1016/s0022-5347(06)00427-7

Cited by 113 publications

(159 citation statements)

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“…With a deleted TP53 gene on one allele and a frame-shift mutation on the other producing a severely truncated non-functional p53 protein, the p53-null PC3 line is a highly metastatic prostate cancer cell line (Table 1). 43,53,54 Stably p53WT transfected PC3 cells (PC3/p53WT) were also employed in this set of experiments to investigate p53's signaling (100 nM) or vehicle control (DMSO) along with serial dilutions of doxorubicin. As seen in Figure 4, we were able to increase the sensitivity of LNCaP cells approximately 100-fold to the effects of doxorubicin when p53 activity was WT.…”

Section: Resultsmentioning

confidence: 99%

p53 expression controls prostate cancer sensitivity to chemotherapy and the MDM2 inhibitor Nutlin-3

et al. 2012

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Section: Resultsmentioning

confidence: 99%

p53 expression controls prostate cancer sensitivity to chemotherapy and the MDM2 inhibitor Nutlin-3

et al. 2012

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“…4A). In PC3 cells, which have a high metastatic potential (20,27), pioglitazone treatment showed no significant effect on invasiveness of the cells compared to that of the control vehicle-treated cells (41.9% Ϯ 2.0% for control-treated cells versus 32.2% Ϯ 8.6% for pioglitazone-treated cells), whereas decreased invasion was observed when PC3 cells were treated with valproic acid (24.0% Ϯ 2.3%). Strikingly, a synergistic effect on the inhibition of invasion was observed when a combination of pioglitazone and valproic acid was used (11.4% Ϯ 3.1%).…”

Section: Synergistic Action Of Ppar␥ Agonists and Hdac Inhibitorsmentioning

confidence: 92%

“…Increased expression of E-cadherin suggested that the combina- Treatments of LNCaP cells with pioglitazone, valproic acid, or both had no effect on the invasive potential of these cells (Fig. 4A), probably due to the low metastatic potential of this cell line (17,27) and a weak percentage of cells invading the Matrigel membrane under basal conditions (Fig. 4A).…”

Section: Synergistic Action Of Ppar␥ Agonists and Hdac Inhibitorsmentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor γ Regulates E-Cadherin Expression and Inhibits Growth and Invasion of Prostate Cancer

Annicotte

Iankova

Miard

et al. 2006

Molecular and Cellular Biology

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Peroxisome proliferator-activated receptor ␥ (PPAR␥) might not be permissive to ligand activation in prostate cancer cells. Association of PPAR␥ with repressing factors or posttranslational modifications in PPAR␥ protein could explain the lack of effect of PPAR␥ ligands in a recent randomized clinical trial. Using cells and prostate cancer xenograft mouse models, we demonstrate in this study that a combination treatment using the PPAR␥ agonist pioglitazone and the histone deacetylase inhibitor valproic acid is more efficient at inhibiting prostate tumor growth than each individual therapy. We show that the combination treatment impairs the bone-invasive potential of prostate cancer cells in mice. In addition, we demonstrate that expression of E-cadherin, a protein involved in the control of cell migration and invasion, is highly up-regulated in the presence of valproic acid and pioglitazone. We show that E-cadherin expression responds only to the combination treatment and not to single PPAR␥ agonists, defining a new class of PPAR␥ target genes. These results open up new therapeutic perspectives in the treatment of prostate cancer.Prostate cancer is the most common form of cancer in men and the second leading cause of cancer deaths. Tumor growth is originally androgen dependent. Androgens exert their effects through activation of the androgen receptor (AR), a member of the hormone nuclear receptor superfamily. In the mature prostatic gland, the AR regulates the expression of genes involved in cell division and proliferation of the epithelial cells (26). The AR is also involved in several other aspects of prostate cellular metabolism, including lipid biosynthesis, and controls the production of specialized secretory proteins with prostate-restricted expression, such as prostate-specific antigen (PSA) (26). When prostate cancer is still hormone dependent, androgen ablation therapy causes regression of the tumor (18), likely through inactivation of the transcription of the AR target genes. However, the durability of this response is inadequate and many men develop recurrent androgen-independent prostate cancer, which has a very poor prognosis (see reference 11 for a review). Other nuclear receptors or locally produced factors that interact with nuclear receptors are likely involved in cell proliferation, differentiation, and apoptosis in the prostate. The peroxisome proliferator-activated receptor ␥ (PPAR␥) is one such factor. PPAR␥ is another member of the hormone nuclear receptor superfamily. As for most of the other members of this family, its activity is regulated by ligands. Prostaglandin J2 and the antidiabetic drugs thiazolidinediones have been determined to be natural and synthetic ligands of PPAR␥, respectively (for a review, see reference 9). PPAR␥ is highly expressed in the adipose tissue and is required for its development through regulation of the expression of adipocyte-specific genes, such as lipoprotein lipase or the fatty acid transport protein aP2. PPAR␥ is expressed in several other tissues in add...

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“…23 Briefly, after total intravenous anesthesia with pentobarbital sodium (30 mg kg À1 ), a midline incision was made in the baenosome. A suspension of SPCA-1 cells (1.0 Â 10 6 ) in 50 ml of PBS containing 20% of growth factor-reduced Matrigel (Becton Dickinson, Barcelona, Spain) was injected into the upper left lobe of lung, and the wound was closed with surgical metal clips.…”

Section: Immunohistochemistry Of Lung Tumorsmentioning

confidence: 99%

Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells

et al. 2008

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Livin, a novel member of the human inhibitors of apoptosis protein (IAP) family, plays an important role in tumor progression and occurrence by inhibiting cell apoptosis. It is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to chemotherapeutic agents. To investigate its possibility as a therapeutic target for human malignancies, we established two genetically different stable tumor cell lines (LoVo and SPCA-1) and RNA interference (RNAi) technique was employed to downregulate Livin expression in two human tumor cell lines. The specific downregulation of Livin expression in tumor cell lines significantly inhibited in vitro cell proliferation and in vivo tumorigenicity. Furthermore, Livin knockdown led to cell arrest in the G 1 /G 0 phase of cell cycle, eventual apoptosis and chemosensitivity enhancement in tumor cells. All these results indicate that RNAi-mediated downregulation of Livin expression can lead to potent antitumor activity and chemosensitizing effects in human cancers.

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RNA Interference-Directed Knockdown of Urokinase Plasminogen Activator and Urokinase Plasminogen Activator Receptor Inhibits Prostate Cancer Cell Invasion, Survival, and Tumorigenicity In Vivo

Cited by 113 publications

References 0 publications

p53 expression controls prostate cancer sensitivity to chemotherapy and the MDM2 inhibitor Nutlin-3

p53 expression controls prostate cancer sensitivity to chemotherapy and the MDM2 inhibitor Nutlin-3

Peroxisome Proliferator-Activated Receptor γ Regulates E-Cadherin Expression and Inhibits Growth and Invasion of Prostate Cancer

Silencing Livin gene expression to inhibit proliferation and enhance chemosensitivity in tumor cells

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