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Increased SNAIL expression and low syndecan levels are associated with high Gleason grade in prostate cancer.

Poblete CE, Fulla J, Gallardo M, Muñoz V, Castellón EA, Gallegos I, Contreras HR - Int. J. Oncol. (2014)

Bottom Line: Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells.Interestingly, syndecan 2 shows no changes associated to histological grade.It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1.

View Article: PubMed Central - PubMed

Affiliation: Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.

ABSTRACT
Prostate cancer (PC) is a leading male oncologic malignancy wideworld. During malignant transformation, normal epithelial cells undergo genetic and morphological changes known as epithelial-mesenchymal transition (EMT). Several regulatory genes and specific marker proteins are involved in PC EMT. Recently, syndecans have been associated with malignancy grade and Gleason score in PC. Considering that SNAIL is mainly a gene repressor increased in PC and that syndecan promoters have putative binding sites for this repressor, we propose that SNAIL might regulate syndecan expression during PC EMT. The aim of this study was to analyze immunochemically the expression of SNAIL, syndecans 1 and 2 and other EMT markers in a tissue microarray (TMA) of PC samples and PC cell lines. The TMAs included PC samples of different Gleason grade and benign prostatic hyperplasia (BPH) samples, as non‑malignant controls. PC3 and LNCaP cell lines were used as models of PC representing different tumorigenic capacities. Semi-quantitative immunohistochemistry was performed on TMAs and fluorescence immunocytochemistry and western blot analysis were conducted on cell cultures. Results show that SNAIL exhibits increased expression in high Gleason specimens compared to low histological grade and BPH samples. Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells. Conversely, syndecan 1, similarly to E-cadherin (a known marker of EMT), shows a decreased expression in high Gleason grades samples and PC3 cells. Interestingly, syndecan 2 shows no changes associated to histological grade. It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1. The mechanism by which SNAIL regulates the expression of syndecan 1 remains to be investigated.

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Related in: MedlinePlus

SNAIL expression and distribution in prostate samples. Immunostaining of SNAIL in samples of different histological grades. (A) Benign prostatic hyperplasia (BPH); (B) low Gleason grade (LGG); (C) medium Gleason grade (MGG); and (D) high Gleason grade (HGG). Inserts, ×1,000. (E) Quantification of SNAIL immunostaining. IOD, integrated optical density. AU, arbitrary units. *P<0.01. Scale bar, 50 μm.
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f2-ijo-44-03-0647: SNAIL expression and distribution in prostate samples. Immunostaining of SNAIL in samples of different histological grades. (A) Benign prostatic hyperplasia (BPH); (B) low Gleason grade (LGG); (C) medium Gleason grade (MGG); and (D) high Gleason grade (HGG). Inserts, ×1,000. (E) Quantification of SNAIL immunostaining. IOD, integrated optical density. AU, arbitrary units. *P<0.01. Scale bar, 50 μm.

Mentions: SNAIL staining is observed mainly in nuclei and shows increased intensity in high Gleason compared to low grade samples (Fig. 2A). H&E dyeing was omitted to avoid interfering with SNAIL nuclear specific staining. Average IOD for each sample showed normal distribution (Kolmogorov-Smirnov P=0.689). Subsequently, the IOD means were compared by ANOVA. Samples with a high Gleason grades show SNAIL-staining IOD means significantly higher (P<0.01) than samples with low Gleason grade and BPH (P<0.0001) (Fig. 2B). Given the normal distribution, the Pearson test established a correlation coefficient of 0.734 between the IOD and the Gleason grade.


Increased SNAIL expression and low syndecan levels are associated with high Gleason grade in prostate cancer.

Poblete CE, Fulla J, Gallardo M, Muñoz V, Castellón EA, Gallegos I, Contreras HR - Int. J. Oncol. (2014)

SNAIL expression and distribution in prostate samples. Immunostaining of SNAIL in samples of different histological grades. (A) Benign prostatic hyperplasia (BPH); (B) low Gleason grade (LGG); (C) medium Gleason grade (MGG); and (D) high Gleason grade (HGG). Inserts, ×1,000. (E) Quantification of SNAIL immunostaining. IOD, integrated optical density. AU, arbitrary units. *P<0.01. Scale bar, 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928469&req=5

f2-ijo-44-03-0647: SNAIL expression and distribution in prostate samples. Immunostaining of SNAIL in samples of different histological grades. (A) Benign prostatic hyperplasia (BPH); (B) low Gleason grade (LGG); (C) medium Gleason grade (MGG); and (D) high Gleason grade (HGG). Inserts, ×1,000. (E) Quantification of SNAIL immunostaining. IOD, integrated optical density. AU, arbitrary units. *P<0.01. Scale bar, 50 μm.
Mentions: SNAIL staining is observed mainly in nuclei and shows increased intensity in high Gleason compared to low grade samples (Fig. 2A). H&E dyeing was omitted to avoid interfering with SNAIL nuclear specific staining. Average IOD for each sample showed normal distribution (Kolmogorov-Smirnov P=0.689). Subsequently, the IOD means were compared by ANOVA. Samples with a high Gleason grades show SNAIL-staining IOD means significantly higher (P<0.01) than samples with low Gleason grade and BPH (P<0.0001) (Fig. 2B). Given the normal distribution, the Pearson test established a correlation coefficient of 0.734 between the IOD and the Gleason grade.

Bottom Line: Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells.Interestingly, syndecan 2 shows no changes associated to histological grade.It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1.

View Article: PubMed Central - PubMed

Affiliation: Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.

ABSTRACT
Prostate cancer (PC) is a leading male oncologic malignancy wideworld. During malignant transformation, normal epithelial cells undergo genetic and morphological changes known as epithelial-mesenchymal transition (EMT). Several regulatory genes and specific marker proteins are involved in PC EMT. Recently, syndecans have been associated with malignancy grade and Gleason score in PC. Considering that SNAIL is mainly a gene repressor increased in PC and that syndecan promoters have putative binding sites for this repressor, we propose that SNAIL might regulate syndecan expression during PC EMT. The aim of this study was to analyze immunochemically the expression of SNAIL, syndecans 1 and 2 and other EMT markers in a tissue microarray (TMA) of PC samples and PC cell lines. The TMAs included PC samples of different Gleason grade and benign prostatic hyperplasia (BPH) samples, as non‑malignant controls. PC3 and LNCaP cell lines were used as models of PC representing different tumorigenic capacities. Semi-quantitative immunohistochemistry was performed on TMAs and fluorescence immunocytochemistry and western blot analysis were conducted on cell cultures. Results show that SNAIL exhibits increased expression in high Gleason specimens compared to low histological grade and BPH samples. Accordingly, PC3 cells show higher SNAIL expression levels compared to LNCaP cells. Conversely, syndecan 1, similarly to E-cadherin (a known marker of EMT), shows a decreased expression in high Gleason grades samples and PC3 cells. Interestingly, syndecan 2 shows no changes associated to histological grade. It is concluded that increased SNAIL levels in advanced PC are associated with low expression of syndecan 1. The mechanism by which SNAIL regulates the expression of syndecan 1 remains to be investigated.

Show MeSH
Related in: MedlinePlus