Abstract
BackgroundCyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers.MethodsIn order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA) on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models.ResultsDownregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo.ConclusionOur data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy.
Highlights
Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis
Control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 small interfering RNA (siRNA) was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo
Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells
Summary
Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. The cell cycle is controlled by a highly conserved family of cyclin-dependent kinases (Cdks) and their regulatory subunits cyclins. Overexpression of cyclin B1 has been reported in various human tumors, such as breast cancer, cervical cancer, gastric cancer, colorectal cancer, head and neck squamous cell carcinoma and non-small-cell lung cancer [3,4,5,6,7,8,9] and its upregulation is closely associated with poor prognosis in various types of cancers including breast cancer [6,10,11]. It is reported that both antibodies and T cells are generated in response to aberrant cyclin B1 expression in tumors like breast cancer [12,13], indicating that overexpressed cyclin B1 could serve as one of the signals to initiate the communication between cancer cells and their microenvironment
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