KLK5 gene expression is severely upregulated in androgen-independent prostate cancer cells after treatment with the chemotherapeutic agents docetaxel and mitoxantrone

Abstract

Kallikrein-related peptidases (KLKs), including KLK5, have been proposed as promising biomarkers for prostate cancer diagnosis and prognosis. In the present study, we report that distinct augmentations (up to 6.4-fold) of KLK5 mRNA expressional levels, calculated via quantitative real-time PCR, occur after treatment of DU145 cells with appropriate concentrations, determined by the MTT method, of docetaxel and mitoxantrone. Our data reveal the endogenous need of prostate cancer cells for modified KLK5 expression to cope with the administration of chemotherapeutic drugs. Furthermore, it is proposed that the expression profile of KLK5 could serve as a putative biomarker for monitoring the treatment response in hormone refractory prostate cancer patients.

Kallikrein-related peptidases (KLKs): a gene family of novel cancer biomarkers

“…KLK5 mRNA expression was also dysregulated in DU145 prostate cancer cells after administration of the antineoplastic agents docetaxel and mitoxantrone. The same study postulated that the expression profi le of KLK5 could serve as a putative biomarker for monitoring the treatment response in hormone refractory prostate cancer patients (152) . According to our unpublished results, modulations of KLK5 and KLK14 mRNA levels were observed in BT-20 breast cancer cells during their apoptosis, induced by their exposure to chemotherapeutic drugs, such as epirubicin, docetaxel, and methotrexate.…”

“…For instance, the combined molecular profi le of the KLK5 and KLK11 genes has been proposed as a new potential molecular biomarker predicting treatment response of prostate cancer (152,153) . In more detail, treatment of PC-3 prostate cancer cells with mitoxantrone, etoposide, doxorubicin and/or carboplatin was shown to induce distinct alterations in the mRNA expression of KLK5 and KLK11 (153) .…”

Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance

“…In contrast to the abovementioned family members, KLK5 (Yousef et al , 2002b ;Korbakis et al , 2009 ) and KLK11 (Nakamura et al , 2003b ;Bi et al , 2010 ) expression levels are correlated with early disease stages and low Gleason scores, highlighting the favorable prognostic nature for patients. Finally, treatment of the androgen-independent prostate cancer cell lines, PC3 and DU145, with broadly used chemotherapeutic agents alters KLK5 expression, indicating its promising value for monitoring of patients ' response to chemotherapy (Thomadaki et al , 2009 ;Mavridis et al , 2010b ).…”

Kallikrein-related peptidase genes as promising biomarkers for prognosis and monitoring of human malignancies

“…Increasing KLK2 serum levels have been associated with residual tumors and biochemical recurrence after the local treatment of patients, designating in this way the presence of a clinical relapse (Ulmert et al, 2009). Additionally, recent promising studies reported severe overexpression of KLK5 gene transcription levels, after treatment of the androgen-independent prostate cancer cell lines PC3 and DU145 with various and broadly used, in clinical practice, chemotherapeutic agents (Thomadaki et al, 2009;Mavridis et al, 2010b). The fact that modulation of the expression levels of these genes were triggered by the presence of anticancer compounds demonstrates the promising clinical value of these family members in the field of monitoring patients' response to chemotherapy in androgenindependent PCa.…”