ABSTRACT
Despite advances in treatment and early detection, breast cancer remains one of the most common types of cancer and is the second leading cause of cancer death after lung cancer in women. Therefore, there is an urgent need to develop new biomarkers and therapeutic targets for the treatment of breast cancer. Based on gene expression profiles and subsequent screening performed in a preliminary study, kinesin family member 20B (KIF20B) was selected as a candidate target molecule, because it was highly and frequently expressed in all subtypes of breast cancer and barely detected in normal tissues. Reverse transcriptionquantitative PCR and western blotting revealed that KIF20B mRNA and protein expression levels were upregulated in most breast cancer cell lines but were scarcely expressed in normal mammary epithelial cells. Immunohistochemical staining of a tissue microarray showed that KIF20B was detected in 145 out of 251 (57.8%) breast cancer tissues. Strong KIF20B expression was significantly related to advanced pathological N stage. Moreover, patients with breast cancer and strong KIF20B expression exhibited a significantly worse prognosis than those with weak or negative KIF20B expression (P<0.0001, logrank test). In multivariate analysis, strong expression was an independent prognostic factor for patients with breast cancer. Furthermore, knockdown of KIF20B expression by small interfering RNA inhibited breast cancer cell proliferation and induced apoptosis. In addition, Matrigel cell invasion assays revealed that the invasiveness of breast cancer cells was significantly decreased by KIF20B silencing. Since KIF20B is an oncoprotein that is strongly expressed in highly malignant clinical breast cancer and serves a pivotal role in breast cancer cell proliferation, survival and invasion, KIF20B could be considered a candidate biomarker for prognostic prediction and a potential molecular target for developing new therapeutics, such as small molecule inhibitors, for a wide variety of breast cancers.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Prognosis , RNA, Small Interfering , MCF-7 Cells , Cell Proliferation/genetics , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Cell Movement/genetics , Kinesins/metabolismABSTRACT
This study aimed to investigate the antimitotic and antiproliferation activities of crude acetone-methanol and aqueous extracts of two marine molluscs commonly found in the Niger Delta region of Nigeria; T.fuscatus and P.aurita, against human cancerous cell lines (DU145, Hep-2, and HCC1395) cell lines in vitro. The antimitotic activity of the extracts was evaluated using Allium cepa root meristematic cells. Antiproliferative activity of the plant extracts against the cancerous cell lines was compared with normal cell line (VeroE6). Doxorubicin was used as a positive control. Gene expression studies using qPCR for the proapoptotic genes, CASP3, CASP8 and P53 were also carried out. The alcohol extract of T.fuscatus (TFAC) exhibited the most promising activity against all the cancer cell lines tested (DU145 IC50 = 96.48 ± 1.36 µg/ml, HCC 1395 IC50 = 61.44 ± 2.45 µg/ml, Hep2 IC50 = 0.52 ± 0.36 µg/ml) and also had the highest selectivity index of 4.94, 7.78 and 921.97 for DU145, HCC 1395 and Hep-2 cells respectively. Furthermore, TFAC was the only extract that significantly upregulated the expression of caspase 3, caspase 8 and P53. Thus, these findings suggest potential exploitation of TFAC as an anticancer agent.
