title: Significant alterations in the expression pattern of kallikrein-related peptidase genes KLK4, KLK5 and KLK14 after treatment of breast cancer cells with the chemotherapeutic agents epirubicin, docetaxel and methotrexate.
abstract: Given that 1.3 million new cases of breast cancer are universally registered among women and approximately 36 % of the patients die annually, the revelation of new predictive markers for treatment efficiency is of vital importance. Recently, our group has depicted that KLK4, KLK5, and KLK14 are differentially expressed in breast carcinoma. The objective of this study was to determine and investigate the expression pattern of the KLK4, KLK5, and KLK14 genes in breast cancer cells after treatment with established chemotherapeutic agents. We evaluated these genes' expression after treatment of the BT-20 cells with epirubicin, docetaxel and methotrexate, determining their cytotoxic effect by MTT and trypan blue assays. The relative quantification of genes' mRNA levels was performed by using the SYBR Green® chemistry, and the HPRT1 served as an endogenous control gene. The drugs triggered apoptosis in treated cells and induced deregulations in the expression of the above KLKs. The most significant alterations were a 12-fold and tenfold increase of KLK5 in docetaxel and methotrexate-treated cells, respectively, while the KLK4 levels decreased by ten-fold in epirubicin, five-fold in docetaxel and twenty-fold in methotrexate treated-cells, compared to the untreated ones. In the case of KLK14 levels, a twofold increase in epirubicin and threefold decrease in methotrexate-treated cells were observed. Present significant alterations in the expression pattern of KLK4, KLK5, and KLK14 could comprise an initial stage for predicting chemotherapy response in breast cancer and should be further investigated as predictive markers in the future.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Athens, 15701, Panepistimiopolis, Athens, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Papachristopoulou
authors.forename: Maroulio
authors.initials: M
authors.lastname: Talieri
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D015251:Epirubicin / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D008727:Methotrexate / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D043823:Taxoids / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D007041:Hypoxanthine Phosphoribosyltransferase; C425336:KLK14 protein, human; C400147:KLK5 protein, human; D007610:Kallikreins; C120801:kallikrein 4; D008727:Methotrexate