Our findings highlight that TIMP-3 induction, as a key epigenetic event modulated by green tea in restoring the MMP:TIMP balance suppresses prostate cancer progression.
This study demonstrated that miR-191 promoted the cell growth and invasion ability in prostate cancer through downregulating TIMP3 and might be a potential target for the biotherapy for PCa.
We evaluated the extent of promoter methylation of genes previously reported as aberrantly methylated in prostate cancer (AIM1, APC, CCND2, GPX3, GSTP1, MCAM, RARβ2, SSBP2 and TIMP3) by quantitative fluorogenic methylation-specific polymerase chain reaction.
The mechanisms involved in TIMP3 transcriptional repression are not fully understood, but evidence suggests that promoter hypermethylation may not be the predominant epigenetic alteration in prostate cancer.
Statistical analysis showed significantly higher methylation in the prostate cancer tissue samples in comparison with matched normal samples for GSTP1 (P = 0.0001 for AA; P = 0.0008 for Cau), RARbeta2 (P < 0.001 for AA and Cau), SPARC (P < 0.0001 for AA and Cau), TIMP3 (P < 0.0001 for AA and Cau), and NKX2-5 (P < 0.0001 for AA; P = 0.003 for Cau).
We sought to determine whether overexpression of tissue inhibitor of metalloproteinase-3 (TIMP-3) could suppress the malignant phenotype of human prostate cancer cell line PC-3M.
The negative effect of TGFbeta1 on ADAMTS-1, -5, -9, and -15 coupled with increases in their inhibitor, TIMP-3 may aid the accumulation of versican in the stromal compartment of the prostate in BPH and prostate cancer.