Expression of potential molecular markers in prostate cancer: Correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

Miyake, Hideaki; Muramaki, Mototsugu; Kurahashi, Toshifumi; Takenaka, Atsushi; Fujisawa, Masato

doi:10.1016/j.urolonc.2008.08.001

Cited by 70 publications

(63 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aurora-A expression in the radical prostatectomy after neoadjuvant hormonal therapy specimens correlated significantly with the preoperative value of the serum PSA, cell-proliferative activity, and pathological stage (23). The biochemical recurrence-free survival in patients with a persistent Aurora-A expression in radical prostatectomy specimens was significantly lower than that in those with a weak Aurora-A expression (23,24). After treatment with Aurora kinase inhibitor VX680, human prostate cancer cell lines (PC3, LNCaP, and mouse C1A) exhibited attenuation of the phosphorylation of histone H3 and reduced survival (25).…”

mentioning

confidence: 88%

“…Previous studies show that Aurora-A is overexpressed in high grade prostatic intraepithelial neoplasia and prostate cancer, and such expression patterns correlate with tumorigenicity, clinical staging, surgical margin status, and seminal vesicle invasion (22)(23)(24). Aurora-A expression in the radical prostatectomy after neoadjuvant hormonal therapy specimens correlated significantly with the preoperative value of the serum PSA, cell-proliferative activity, and pathological stage (23).…”

mentioning

confidence: 92%

See 1 more Smart Citation

Phosphorylation and Activation of Androgen Receptor by Aurora-A

Shu

Liu

Coppola

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Aurora-A kinase is frequently overexpressed/activated in various types of human malignancy, including prostate cancer. In this study, we demonstrate elevated levels of Aurora-A in androgen-refractory LNCaP-RF but not androgen-sensitive LNCaP cells, which prompted us to examine whether Aurora-A regulates the androgen receptor (AR) and whether elevated Aurora-A is involved in androgen-independent cell growth. We show that ectopic expression of Aurora-A induces AR transactivation activity in the presence and absence of androgen. Aurora-A interacts with AR and phosphorylates AR at Thr 282 and Ser 293 in vitro and in vivo. Aurora-A induces AR transactivation activity in a phosphorylation-dependent manner. Ectopic expression of Aurora-A in LNCaP cells induces prostate-specific antigen expression and cell survival, whereas knockdown of Aurora-A sensitizes LNCaP-RF cells to apoptosis and cell growth arrest. These data indicate that AR is a substrate of Aurora-A and that elevated Aurora-A could contribute to androgen-independent cell growth by phosphorylation and activation of AR.

show abstract

mentioning

confidence: 88%

mentioning

confidence: 92%

Phosphorylation and Activation of Androgen Receptor by Aurora-A

Shu

Liu

Coppola

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…32 The HSPB1 level increases after androgen suppression and is cytoprotective in hormone-refractory PCa. 33,34 In our study, the HSPB1 increase was shown by iTRAQ analysis and qRT-PCR, suggesting its implication in the natural progression of PCa and the tumour response to DES.…”

Section: Discussionsupporting

confidence: 54%

Quantitative proteomic determination of diethylstilbestrol action on prostate cancer

Bigot¹,

Mouzat²,

Lebdai³

et al. 2013

Asian J Androl

View full text Add to dashboard Cite

Diethylstilbestrol (DES) has a direct cellular mechanism inhibition on prostate cancer. Its action is independent from the oestrogen receptors and is preserved after a first-line hormonal therapy. We aimed to identify proteins involved in the direct cellular inhibition effects of DES on prostate cancer. We used a clonogenic assay to establish the median lethal concentration of DES on 22RV1 cells. 22RV1 cells were exposed to standard and DES-enriched medium. After extraction, protein expression levels were obtained by two-dimensional differential in-gel electrophoresis (2D-DIGE) and isotope labelling tags for relative and absolute quantification (iTRAQ). Proteins of interest were analysed by quantitative RT-PCR and western blotting. The differentially regulated proteins (P,0.01) were interrogated against a global molecular network based on the ingenuity knowledge base. The 2D-DIGE analyses revealed DES-induced expression changes for 14 proteins (.1.3 fold; P,0.05). The iTRAQ analyses allowed the identification of 895 proteins. Among these proteins, 65 had a modified expression due to DES exposure (i.e., 23 overexpressed and 42 underexpressed). Most of these proteins were implicated in apoptosis and redox processes and had a predicted mitochondrial expression. Additionally, ingenuity pathway analysis placed the OAT and HSBP1 genes at the centre of a highly significant network. RT-PCR confirmed the overexpression of OAT (P50.006) and HSPB1 (P50.046).

show abstract

“…However, after the establishment of the tumor, an increase in expression of MMP2 may be involved in tumor differentiation, which explains the association of elevated MMP2 expression in highgrade tumors. Miyake et al (2010) (20), using immunohistochemistry showed that in univariate analysis MMP2 expression was significantly associated with biochemical recurrence, demonstrating the importance of this gene in the progression of PCa. At the post-translational level, MMPs are under the control of specific tissue inhibitors (TIMPs) that bind proximal to the catalytic domain of the MMPs, preventing substrate binding.…”

Section: Discussionmentioning

confidence: 97%

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

et al. 2012

View full text Add to dashboard Cite

Prostate cancer (PCa) is a common disease with a multifactorial and complex etiology. It is the most common malignancy in the male and the second leading cause of death in many countries, including Brazil. Estimates for 2011 indicate that 903,500 new cases and 258,400 deaths relatVol. 38 (2): 167-174; March -April, 2012 Objective: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specifi c regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specifi c pattern and if the profi les are related to prognosis and clinical outcome of prostate cancer (PCa). Materials and Methods: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profi le of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the fi nal outcome of the PCa. Results: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (≥ 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). Conclusion: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior. Underexpression of MMP-2 and its

show abstract

Expression of potential molecular markers in prostate cancer: Correlation with clinicopathological outcomes in patients undergoing radical prostatectomy

Cited by 70 publications

References 17 publications

Phosphorylation and Activation of Androgen Receptor by Aurora-A

Phosphorylation and Activation of Androgen Receptor by Aurora-A

Quantitative proteomic determination of diethylstilbestrol action on prostate cancer

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

Contact Info

Product

Resources

About