Down‐regulated expression of prostasin in high‐grade or hormone‐refractory human prostate cancers

Takahashi, Satoru; Suzuki, Shugo; Inaguma, Shingo; Ikeda, Yoshihisa; Cho, Young‐Man; Hayashi, Norio; Inoue, Takahiro; Sugimura, Yoshiki; Nakatani, Naoki; Fujita, Tamio; Chao, Julie; Ushijima, Toshikazu; Shirai, Tomoyuki

doi:10.1002/pros.10178

Cited by 49 publications

(36 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, PRSS8 (prostasin) was reportedly up-regulated in many microarray studies that used bulk tissues (17), but in our experiments, expression of this gene was either unchanged or downregulated in some PCs as compared with normal epithelium. PRSS8 is predominantly expressed in normal prostatic epithelial cells; several studies using in situ techniques have revealed its down-regulation in PC cells (18,19). These observations make clear that contamination of cancer tissues with stromal cells or normal prostate epithelium can mislead efforts to understand the molecular pathology of PC; therefore, microdissection is definitely required for precision in microarray analyses of PCs.…”

Section: Molecular Features Of the Transition From Pins To Pcsmentioning

confidence: 99%

Molecular Features of the Transition from Prostatic Intraepithelial Neoplasia (PIN) to Prostate Cancer

et al. 2004

View full text Add to dashboard Cite

To characterize the molecular feature in prostate carcinogenesis and the putative transition from prostatic intraepithelial neoplasia (PIN) to invasive prostate cancer (PC), we analyzed gene-expression profiles of 20 PCs and 10 high-grade PINs with a cDNA microarray representing 23,040 genes. Considering the histological heterogeneity of PCs and the minimal nature of PIN lesions, we applied laser microbeam microdissection to purify populations of PC and PIN cells, and then compared their expression profiles with those of corresponding normal prostatic epithelium also purified by laser microbeam microdissection. A hierarchical clustering analysis separated the PC group from the PIN group, except for three tumors that were morphologically defined as one very-high-grade PIN and two low-grade PCs, suggesting that PINs and PCs share some molecular features and supporting the hypothesis of PIN-to-PC transition. On the basis of this hypothesis, we identified 21 up-regulated genes and 63 down-regulated genes commonly in PINs and PCs compared with normal epithelium, which were considered to be involved in the presumably early stage of prostatic carcinogenesis. They included AMACR, OR51E2, RODH, and SMS. Furthermore, we identified 41 up-regulated genes and 98 down-regulated genes in the transition from PINs to PCs; those altered genes, such as POV1, CDKN2C, EPHA4, APOD, FASN, ITGB2, LAMB2, PLAU, and TIMP1, included elements that are likely to be involved in cell adhesion or the motility of invasive PC cells. The down-regulation of EPHA4 by small interfering RNA in PC cells lead to attenuation of PC cell viability. These data provide clues to the molecular mechanisms underlying prostatic carcinogenesis, and suggest candidate genes the products of which might serve as molecular targets for the prevention and treatment of PC.

show abstract

Section: Molecular Features Of the Transition From Pins To Pcsmentioning

confidence: 99%

Molecular Features of the Transition from Prostatic Intraepithelial Neoplasia (PIN) to Prostate Cancer

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Significant overexpression of hepsin is common in 90% of PCa tumours, correlating with Gleason score, serum PSA levels as well as early relapse following radical prostatectomy (Dhanasekaran et al, 2001; Goel et al, 2011). In contrast, prostasin levels are high in normal prostate epithelial cells and decrease in PCa (Takahashi et al, 2003). We therefore tested the hypothesis that TMEFF2 is cleaved at different sites by ADAMs and TTSPs and we provide evidence of complex TMEFF2 proteolysis by these proteases that may impact the biological function of TMEFF2 reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

TMEFF2 shedding is regulated by oxidative stress and mediated by ADAMs and transmembrane serine proteases implicated in prostate cancer

Gaweł-Bęben

Ali

Ellis

et al. 2017

Cell Biology International

View full text Add to dashboard Cite

TMEFF2 is a type I transmembrane protein with two follistatin (FS) and one EGF‐like domain over‐expressed in prostate cancer; however its biological role in prostate cancer development and progression remains unclear, which may, at least in part, be explained by its proteolytic processing. The extracellular part of TMEFF2 (TMEFF2‐ECD) is cleaved by ADAM17 and the membrane‐retained fragment is further processed by the gamma‐secretase complex. TMEFF2 shedding is increased with cell crowding, a condition associated with the tumour microenvironment, which was mediated by oxidative stress signalling, requiring jun‐kinase (JNK) activation. Moreover, we have identified that TMEFF2 is also a novel substrate for other proteases implicated in prostate cancer, including two ADAMs (ADAM9 and ADAM12) and the type II transmembrane serine proteinases (TTSPs) matriptase‐1 and hepsin. Whereas cleavage by ADAM9 and ADAM12 generates previously identified TMEFF2‐ECD, proteolytic processing by matriptase‐1 and hepsin produced TMEFF2 fragments, composed of TMEFF2‐ECD or FS and/or EGF‐like domains as well as novel membrane retained fragments. Differential TMEFF2 processing from a single transmembrane protein may be a general mechanism to modulate transmembrane protein levels and domains, dependent on the repertoire of ADAMs or TTSPs expressed by the target cell.

show abstract

“…Hepsinencoding gene, Hpn, is among the most consistently and quantitatively overexpressed genes in human prostate cancer, as detected by cDNA microarray and tissue array assays, and hepsin is the most reliable single marker to distinguish prostatic neoplasia from benign prostate hyperplasia (21)(22)(23). Prostasin, one glycosylphosphatidylinositol-anchored serine protease, has been reported to be upregulated in ovarian cancer but downregulated in high-grade prostate cancer (17,24,25). Therefore, HAI-1 may contribute to the prevention of cancer growth and progression via inhibition of these serine protease activities.…”

Section: Introductionmentioning

confidence: 99%

Hepatocyte growth factor activator inhibitor type-1 in cancer: Advances and perspectives (Review)

Zheng¹,

Wu²,

Cao³

et al. 2014

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Cancer is one of the most common diseases, with high morbidity and mortality rates. Large-scale efforts have been made to understand the pathogenesis of the disease, particularly in the advanced stages, in order to develop effective therapeutic approaches. Hepatocyte growth factor activator inhibitor type-1 (HAI-1), also known as serine protease inhibitor Kunitz type 1, inhibits the activity of several trypsin-like serine proteases. In particular, HAI-1 suppresses hepatocyte growth factor (HGF) activator and matriptase, resulting in subsequent inhibition of HGF/scatter factor and macrophage-stimulating protein (MSP). HGF and MSP are involved in cancer development and progression, via the receptors Met receptor tyrosine kinase (RTK) and Ron RTK, respectively. Therefore, HAI-1-mediated downregulation of HGF and MSP signaling may suppress tumorigenesis and progression in certain types of cancers. Abnormal HAI-1 expression levels have been observed in various types of human cancer. The exact function of HAI-1 in cancer pathogenesis, however, has not been fully elucidated. In this review, the focus is on the potential impact of aberrant HAI-1 expression levels on tumorigenesis and progression, the underlying mechanisms, and areas that require further investigation to clarify the precise role of HAI-1 in cancer.

show abstract

Down‐regulated expression of prostasin in high‐grade or hormone‐refractory human prostate cancers

Abstract: These results suggest that prostasin cannot be regarded as a prognostic indicator for human prostate cancer although it may be a useful marker for tumor differentiation.

Cited by 49 publications

References 13 publications

Molecular Features of the Transition from Prostatic Intraepithelial Neoplasia (PIN) to Prostate Cancer

Molecular Features of the Transition from Prostatic Intraepithelial Neoplasia (PIN) to Prostate Cancer

TMEFF2 shedding is regulated by oxidative stress and mediated by ADAMs and transmembrane serine proteases implicated in prostate cancer

Hepatocyte growth factor activator inhibitor type-1 in cancer: Advances and perspectives (Review)

Contact Info

Product

Resources

About