Do fasudil and Y-27632 affect the level of transient receptor potential (TRP) gene expressions in breast cancer cell lines?
Breast cancer (BC) is the most frequent cancer type in women, and the mortality rate is high especially in metastatic disease. Ion channels such as the transient receptor potential (TRP) channels correlate with malignant growth and cancer progression. Hence, some authors have suggested that the expression levels of TRP channels may be used as a marker in the diagnosis and predicting the prognosis of BC. Also, in some recent studies, targeting TRP channels are suggested as a novel treatment strategy in BC. The aim of this study was to investigate the effect of two Rho-kinase (ROCK) inhibitors, fasudil and Y-27632, on the expression levels of TRP channel genes in breast cancer cell lines (ZR-75-1, MCF7, and MDA-MB-231) and breast epithelial cell line (hTERT-HME1). The expression levels of TRP genes were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We found that fasudil had reduced the TRPC1, TRPV2 expression levels in the ZR-75-1, MCF7, and MDA-MB-231 cell lines. On the other hand, fasudil and Y-27632 had reduced TRPM6 expression levels in all cell lines. Y-27632 increased the expression levels of TRPC7 in all cell lines. In conclusion, this is the first study demonstrating that the inhibition of ROCK pathway changes the expression levels of some TRP genes. Also, our study has firstly shown that the expression levels of the TRP genes which are suggested as a diagnostic and prognostic biomarker in BC, were changed with the treatment of fasudil and Y-27632.
Faculty of Medicine, Department of Medical Biology, Mustafa Kemal University, Antakya, Hatay, 31034, Turkey, bgogebakan@gmail.com.
Bulent
B
Gogebakan
Recep
R
Bayraktar
Ali
A
Suner
Ozan
O
Balakan
Mustafa
M
Ulasli
Muzeyyen
M
Izmirli
Serdar
S
Oztuzcu
Celaletdin
C
Camci
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D011725:Pyridines / Q000494:pharmacology*; D050052:TRPC Cation Channels / Q000235:genetics; D050053:TRPM Cation Channels / Q000235:genetics; D050051:Transient Receptor Potential Channels / Q000235:genetics*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology
D000577:Amides; D011725:Pyridines; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D050053:TRPM Cation Channels; C459082:TRPM6 protein, human; D050051:Transient Receptor Potential Channels; C096351:transient receptor potential cation channel, subfamily C, member 1; C108830:Y 27632; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil