Trichostatin A reduced phospholipase C gamma-1 transcript and protein contents in MCF-7 breast cancer cells.
ABSTRACT It has recently been demonstrated that phospholipase C gamma-1 (PLCγ1) activation may contribute to breast carcinoma cell motility and their metastasis. Employing MCF-7 breast cancer cells, we showed the effect of trichostatin A (TSA) on the cellular contents of the PLCγ1 molecule. Using reverse transcription, real-time quantitative PCR and western blot analysis, we demonstrated that TSA reduced the PLCγ1 transcript and protein levels in MCF-7 cells. We also found that TSA decreased the half-life of the PLCγ1 transcript from approximately 7hours to 5hours. Moreover, we observed that protein synthesis appears to be essential in the TSA reduction of PLCγ1 mRNA stability. Since PLCγ1 activation is considered a key factor in the initiation of events that increase malignant cell motility, our observations may support the validity of TSA in anticancer studies.
- SourceAvailable from: Mauro Piantelli[show abstract] [hide abstract]
ABSTRACT: Cell motility and invasion play an essential role in the development of metastasis. Evidence suggests that the enzyme phospholipase Cgamma1 (PLCgamma1) may be involved in tumor progression and possibly development of metastasis. In this study, we show that down-regulation of PLCgamma1 expression severely impairs activation of the small GTP-binding protein Rac and cell invasion in breast cancer cell lines and U87 in vitro. Experimental metastasis assays in nude mice show that inducible knockdown of PLCgamma1 strongly inhibits development of MDA-MB-231-derived lung metastasis and reverts metastasis formation. In addition, analysis of 60 breast cancer patients' tissues revealed an increase of PLCgamma1 expression in metastasis compared with the primary tumor in 50% of tissues analyzed. These data show a critical role of PLCgamma1 in the metastatic potential of cancer cells, and they further indicate that PLCgamma1 inhibition has a therapeutic potential in the treatment of metastasis dissemination.Cancer Research 01/2009; 68(24):10187-96. · 8.65 Impact Factor