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Epigenetic modification suppresses proliferation, migration and invasion of urothelial cancer cell lines

View Article: PubMed Central - PubMed

ABSTRACT

Epigenetic approaches offer additional therapeutic options, including apoptosis induction, modification of cell cycle regulating proteins and the re-expression of pharmaceutical targets, such as hormone receptors. The present study analyzed the effect of the epigenetic modifiers 5-aza-2′-deoxycytidine and Trichostatin A on the proliferative, migratory and invasive behavior of four urinary bladder cancer cell lines (RT-4, RT-112, VMCUB-1 and T-24), and the expression of various matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). Cell proliferation, migration and invasion assays revealed that treatment with the two epigenetic modifiers resulted in proliferation inhibition in all cell lines, and migration and invasion inhibition in RT-4, RT-112 and T-24 cell lines. Quantitative polymerase chain reaction demonstrated that the mRNA expression of a broad selection of MMPs and their TIMPs was induced in all cell lines, and MMP-14 mRNA expression was suppressed in all cell lines, with the exception of RT-4. In conclusion, epigenetic modifications suppressed the motility and invasiveness of three out of four urothelial cancer cell lines. The inhibitory effect on cell motility appears to be crucial for reduced invasive properties. However, even a broad spectrum of mRNA analysis does not sufficiently explain the loss of invasiveness, as it does not allow for functional conclusions. Further complex urothelial tumour models should be applied to investigate whether epigenetic therapeutic approaches may be an option in urothelial cancer.

No MeSH data available.


Related in: MedlinePlus

MMPs, TIMPs and mRNA expression in 5-aza-2′-deoxycytidin and Trichostatin A-treated human urinary bladder cancer (A) RT-4 (B) RT-112, (C) VMCUB-1 and (D) T-24 cells, using quantitative polymerase chain reaction. Values >100 have been equated with 100. The color of the column indicates the level of mRNA expression, according to the Cq. MMP-9 did not exhibit any expression and is not included. MMP, Matrix metalloproteinase; TIMP, tissue inhibitor matrix metalloproteinase; EMMPRIN, extracellular matrix metalloproteinase inducer.
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f4-ol-0-0-4877: MMPs, TIMPs and mRNA expression in 5-aza-2′-deoxycytidin and Trichostatin A-treated human urinary bladder cancer (A) RT-4 (B) RT-112, (C) VMCUB-1 and (D) T-24 cells, using quantitative polymerase chain reaction. Values >100 have been equated with 100. The color of the column indicates the level of mRNA expression, according to the Cq. MMP-9 did not exhibit any expression and is not included. MMP, Matrix metalloproteinase; TIMP, tissue inhibitor matrix metalloproteinase; EMMPRIN, extracellular matrix metalloproteinase inducer.

Mentions: All data regarding smRNA expression levels and the effect of epigenetic modifiers are summarized in Fig. 4 and Table II.


Epigenetic modification suppresses proliferation, migration and invasion of urothelial cancer cell lines
MMPs, TIMPs and mRNA expression in 5-aza-2′-deoxycytidin and Trichostatin A-treated human urinary bladder cancer (A) RT-4 (B) RT-112, (C) VMCUB-1 and (D) T-24 cells, using quantitative polymerase chain reaction. Values >100 have been equated with 100. The color of the column indicates the level of mRNA expression, according to the Cq. MMP-9 did not exhibit any expression and is not included. MMP, Matrix metalloproteinase; TIMP, tissue inhibitor matrix metalloproteinase; EMMPRIN, extracellular matrix metalloproteinase inducer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998357&req=5

f4-ol-0-0-4877: MMPs, TIMPs and mRNA expression in 5-aza-2′-deoxycytidin and Trichostatin A-treated human urinary bladder cancer (A) RT-4 (B) RT-112, (C) VMCUB-1 and (D) T-24 cells, using quantitative polymerase chain reaction. Values >100 have been equated with 100. The color of the column indicates the level of mRNA expression, according to the Cq. MMP-9 did not exhibit any expression and is not included. MMP, Matrix metalloproteinase; TIMP, tissue inhibitor matrix metalloproteinase; EMMPRIN, extracellular matrix metalloproteinase inducer.
Mentions: All data regarding smRNA expression levels and the effect of epigenetic modifiers are summarized in Fig. 4 and Table II.

View Article: PubMed Central - PubMed

ABSTRACT

Epigenetic approaches offer additional therapeutic options, including apoptosis induction, modification of cell cycle regulating proteins and the re-expression of pharmaceutical targets, such as hormone receptors. The present study analyzed the effect of the epigenetic modifiers 5-aza-2′-deoxycytidine and Trichostatin A on the proliferative, migratory and invasive behavior of four urinary bladder cancer cell lines (RT-4, RT-112, VMCUB-1 and T-24), and the expression of various matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). Cell proliferation, migration and invasion assays revealed that treatment with the two epigenetic modifiers resulted in proliferation inhibition in all cell lines, and migration and invasion inhibition in RT-4, RT-112 and T-24 cell lines. Quantitative polymerase chain reaction demonstrated that the mRNA expression of a broad selection of MMPs and their TIMPs was induced in all cell lines, and MMP-14 mRNA expression was suppressed in all cell lines, with the exception of RT-4. In conclusion, epigenetic modifications suppressed the motility and invasiveness of three out of four urothelial cancer cell lines. The inhibitory effect on cell motility appears to be crucial for reduced invasive properties. However, even a broad spectrum of mRNA analysis does not sufficiently explain the loss of invasiveness, as it does not allow for functional conclusions. Further complex urothelial tumour models should be applied to investigate whether epigenetic therapeutic approaches may be an option in urothelial cancer.

No MeSH data available.


Related in: MedlinePlus