J Vet Sci.  2015 Sep;16(3):281-287. 10.4142/jvs.2015.16.3.281.

Decreased expression of Toll-like receptor 4 and 5 during progression of prostate transformation in transgenic adenocarcinoma of mouse prostate mice

• Han JH
• Park JH
• Kim BY
• Chang SN
• Kim TH
• Park JH
• Kim DJ

• KMID: 2344300
• DOI: http://doi.org/10.4142/jvs.2015.16.3.281

Abstract

Chronic inflammation has been considered an important risk factor for development of prostate cancer. Toll-like receptors (TLRs) recognize microbial moieties or endogenous molecules and play an important role in the triggering and promotion of inflammation. In this study, we examined whether expression of TLR4 and TLR5 was associated with progression of prostate transformation in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The expression of TLR4 and TLR5 was evaluated by immunohistochemisty in formalin-fixed paraffin-embedded prostate tissue from wild-type (WT) and TRAMP mice. Normal prostate tissue from WT mice showed strong expression of TLR4 and TLR5. However, TLR4 expression in the prostate tissue from TRAMP mice gradually decreased as pathologic grade became more aggressive. TLR5 expression in the prostate tissue from TRAMP mice also decreased in low-grade prostate intraepithelial neoplasia (PIN), high-grade PIN and poorly differentiated adenocarcinoma. Overall, our results suggest that decreased expression of TLR4 and TLR5 may contribute to prostate tumorigenesis.

Keyword

prostate cancer; Toll-like receptor 4; Toll-like receptor 5; transgenic adenocarcinoma of mouse prostate

MeSH Terms

Adenocarcinoma/etiology/*genetics
Animals
Cell Transformation, Neoplastic
Disease Progression
*Gene Expression Regulation, Neoplastic
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Prostatic Neoplasms/etiology/*genetics
Toll-Like Receptor 4/*genetics/metabolism
Toll-Like Receptor 5/*genetics/metabolism
Toll-Like Receptor 4
Toll-Like Receptor 5

Figure

• 

  Fig. 1 Pathologic grade of transgenic adenocarcinoma of mouse prostate (TRAMP). Prostate tissues from wild-type (WT) and TRAMP mice were fixed in 10% formalin for 24 h, then processed in a standard alcohol-xylene series. The tissues were subsequently embedded in paraffin, after which 3 µm sections were prepared and stained with hematoxylin and eosin. Images of normal prostate tissue from WT mice (A) and low-grade prostate intraepithelial neoplasia (PIN) (B), high-grade PIN (C), poorly differentiated adenocarcinoma (D) and phylloides-like cancer (E) from TRAMP mice. Magnification: 400× (A-E), 100× (inset).

• 

  Fig. 2 Cytokeratin 8 expression in pathologic grades of TRAMP. Sections from Fig. 1 were incubated with anti-cytokeratin 8 antibody. Images of normal prostate tissue from WT mice (A) and low-grade PIN (B), high-grade PIN (C), poorly differentiated adenocarcinoma (D). Magnification: 400× (A-E), 100× (inset).

• 

  Fig. 3 Synaptophysin expression in pathologic grades of TRAMP prostate. Sections from Figure 1 were incubated with antisynaptophysin antibody. Images of normal prostate tissue from WT mice (A) and low-grade PIN (B), high-grade PIN (C), poorly differentiated adenocarcinoma (D). Magnification: 400× (A-D), 100× (inset).

• 

  Fig. 4 TLR4 expression in pathologic grades of TRAMP prostate. Sections from Figure 1 were incubated with anti-TLR4 antibody. Images of normal prostate tissue from WT mice (A) and low-grade PIN (B), high-grade PIN (C), poorly differentiated adenocarcinoma (D). The intensity of TLR4 immunostaining in each pathologic grade is shown (E). Intensity of TLR4 immunostaining was measured in an average of three fields and is presented as the mean ± standard deviation (SD; *p < 0.05, **p < 0.01, and ***p < 0.001). Normal, normal prostate; Low PIN, low-grade PIN; High PIN, high-grade PIN; AC, poorly differentiated adenocarcinoma. Magnification: 400× (A-D), 100× (inset).

• 

  Fig. 5 TLR5 expression in pathologic grades of TRAMP prostate. Sections from Figure 1 were incubated with anti-TLR5 antibody. Images of normal prostate tissue from WT mice (A) and low-grade PIN (B), high-grade PIN (C), poorly differentiated adenocarcinoma (D). The intensity of TLR5 immunostaining in each pathologic grade is shown (E). Intensity of TLR5 immunostaining was measured in an average of three fields and is presented as mean ± SD (*p < 0.05 and **p < 0.01). (A-D) 400× magnification, (inset) 100× magnification.

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