Thrombin receptor expression is upregulated in prostate cancer

Kaushal, Varsha; Kohli, Manish; Dennis, Richard A.; Siegel, Eric R.; Chiles, Walter W; Mukunyadzi, Perkins

doi:10.1002/pros.20326

Cited by 60 publications

(84 citation statements)

References 45 publications

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“…From the two derived cDNAs, the target gene, encoding PAR1 receptor known to be expressed and regulated in prostate carcinoma and cell lines (Kaushal et al, 2006;Yuan and Lin, 2004), was quantified, as well as two dedicated HKGs, namely TBP and PPIA. Both were chosen for their discrepant expression under variable hypoxic conditions: TBP showed one of the greatest stability in LNCaP cell line whereas PPIA was one of the less stable HKG in this model system.…”

Section: Gene Expression Varies According To the Hkg Usedmentioning

confidence: 99%

‘Desperate house genes’: the dramatic example of hypoxia

Caradec

Sirab

Keumeugni³

et al. 2010

Br J Cancer

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BACKGROUND: Microenvironmental conditions in normal or tumour tissues and cell lines may interfere on further biological analysis. To evaluate transcript variations carefully, it is common to use stable housekeeping genes (HKG) to normalise quantitative microarrays or real-time polymerase chain reaction results. However, recent studies argue that HKG fluctuate according to tissues and treatments. So, as an example of HKG variation under an array of conditions that are common in the cancer field, we evaluate whether hypoxia could have an impact on HKG expression. METHODS: Expression of 10 commonly used HKG was measured on four cell lines treated with four oxygen concentrations (from 1 to 20%). RESULTS: Large variations of HKG transcripts were observed in hypoxic conditions and differ along with the cell line and the oxygen concentration. To elect the most stable HKG, we compared the three statistical means based either on PCR cycle threshold coefficient of variation calculation or two specifically dedicated software. Nevertheless, the best HKG dramatically differs according to the statistical method used. Moreover, using, as a reference, absolute quantification of a target gene (here the proteinase activating receptor gene 1 (PAR1) gene), we show that the conclusions raised about PAR1 variation in hypoxia can totally diverge according to the selected HKG used for normalisation. CONCLUSION: The choice of a valid HKG will determine the relevance of the results that will be further interpreted, and so it should be seriously considered. The results of our study confirm unambiguously that HKG variations must be precisely and systematically determined before any experiment for each situation, to obtain reliable normalised results in the experimental setting that has been designed. Indeed, such assay design, functional for all in vitro systems, should be carefully evaluated before any extension to other experimental models including in vivo ones.

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Section: Gene Expression Varies According To the Hkg Usedmentioning

confidence: 99%

‘Desperate house genes’: the dramatic example of hypoxia

Caradec

Sirab

Keumeugni³

et al. 2010

Br J Cancer

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“…It has been reported that PAR-1 was expressed highly in many types of cancer, such as breast cancer (9), malignant melanoma (10), prostate cancer (11), colon cancer (12), lung cancer (13), oral squamous cell carcinoma (14), esophageal cancer (15), and renal cell carcinoma (16). Early study by Even-Ram et al (9) demonstrated that PAR-1 expression levels were correlated with degree of invasiveness in both primary breast tissue specimens and established cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

The activation of protease-activated receptor 1 mediates proliferation and invasion of nasopharyngeal carcinoma cells

et al. 2012

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Abstract. Protease-activated receptor 1 (PAR-1) is a G-coupled membrane protein, which is involved in physiological and malignant invasion processes. It is activated by serine proteases such as thrombin through a unique form or by specific synthetic peptides. In this study, we determined the expression of PAR-1 in five nasopharyngeal carcinoma (NPC) cell lines with different characteristics of invasiveness and metastasis, and found that the levels of PAR-1 expression were higher in invasive or metastatic cell lines than those in low invasive or metastatic ones. Of the five NPC cell lines, CNE1-LMP1 cells had the highest expression levels of PAR-1, which was mainly distributed at the membrane and in the cytoplasm of tumor cells. Further study showed that the thrombin receptor synthetic activating peptide SFLLRN could stimulate the growth of CNE1-LMP1 cells in a dosedependent manner. However, thrombin itself had a dual effect on the proliferation of NPC cells. Concentrations of thrombin in the range of 0.1-0.5 U/ml promoted cell growth, but concentrations higher than 0.5 U/ml impaired cell growth. Moreover, thrombin and SFLLRN also enhanced the invasive capabilities of CNE1-LMP1 cells in vitro, and this was partly due to enhancing the activities of MMP-2 and MMP-9. Our findings suggest that PAR-1 may contribute to the growth and invasive potential of NPC cells.

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“…Studies have shown that expression of PAR1 is clearly increased in advanced prostate cancer (47)(48)(49). The activation of PARs promotes proliferation, invasion, and release of angiogenic factors by cancer cells (50,51), and kallikreins are enzymes that are known to cleave this receptor with a specificity similar to thrombin (52,53).…”

Section: Discussionmentioning

confidence: 99%

“…Death-The effect of rBbKIm on the viability of DU145 and PC3 cells was analyzed by the MTT assay at different time points (24,48, and 72 h) (Fig. 1).…”

Section: Action Of Rbbkim and Sbti On Cell Viability And Cellmentioning

confidence: 99%

The Impaired Viability of Prostate Cancer Cell Lines by the Recombinant Plant Kallikrein Inhibitor

Ferreira

Diniz

Paula

et al. 2013

Journal of Biological Chemistry

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Background: Kallikreins play a pivotal role in establishing prostate cancer. Results: In contrast to the classical Kunitz plant inhibitor SbTI, the recombinant kallikrein inhibitor (rBbKIm) led to prostate cancer cell death, whereas fibroblast viability was not affected. Conclusion: rBbKIm shows selective cytotoxic effect and angiogenesis inhibition against prostate cancer cells. Significance: New actions of rBbKIm may contribute to understanding the mechanisms of prostate cancer.

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Thrombin receptor expression is upregulated in prostate cancer

Cited by 60 publications

References 45 publications

‘Desperate house genes’: the dramatic example of hypoxia

‘Desperate house genes’: the dramatic example of hypoxia

The activation of protease-activated receptor 1 mediates proliferation and invasion of nasopharyngeal carcinoma cells

The Impaired Viability of Prostate Cancer Cell Lines by the Recombinant Plant Kallikrein Inhibitor

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