Nek2A contributes to tumorigenic growth and possibly functions as potential therapeutic target for human breast
Shuling Wang1, Weidong Li, Ning Liu
1Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Abstract:
Nek2A (NIMA-related kinases 2A) has been known as an important centrosome regulatory factor. The aim of this study was to investigate the expression of Nek2A and the role it played in different stages of breast cancer. We detected the expression of Nek2A in both mRNA and protein levels in MCF10 cell lines including MCF-10A, MCF-10DCIS.com, MCF-10CA1a and in human breast samples which contained normal breast tissue (NBT), breast ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). Our study revealed that the mRNA and protein expression of Nek2A were significantly up-regulated in MCF-10DCIS.com and MCF-10CA1a cell lines as well as in human primary breast cancer tissue (DCIS and IDC). Our study also presented a correlation between Nek2A mRNA expression and some clinic pathological factors. We found that Nek2A mRNA expression was associated with molecular subtypes, ER, PR and Ki-67 immunoreactivity (P<0.05) in DCIS and associated with histological grade, lymph node metastasis, molecular subtypes, c-erbB-2, and Ki-67 expression (P<0.05) in IDC. In addition, we observed that ectopic expression of Nek2A in "normal" immortalized MCF-10A breast epithelial cell resulted in increased Nek2A which lead to abnormal centrosomes. Furthermore, knockdown of Nek2A in MCF-10DCIS.com could remarkably inhibit cell proliferation and induce cell cycle arrest in MCF-10DCIS.com cell line. These data suggested that Nek2A might bear a close relationship with development and progression of breast carcinoma, and highlighted its role as a novel potential biomarker for diagnosis and a possible therapeutic target for human breast cancer especially for DCIS.
Insights
NIMA-related kinases 2A (Nek2A) is upregulated in breast cancer, correlating with disease progression and poor prognostic factors. Inhibiting Nek2A reduces cancer cell proliferation, suggesting it as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- NIMA-related kinases 2A (Nek2A) is a key regulator of centrosome function.
- Aberrant centrosome regulation is implicated in cancer development.
Purpose of the Study:
- To investigate Nek2A expression in breast cancer.
- To determine the role of Nek2A in breast cancer progression.
- To evaluate Nek2A as a potential diagnostic biomarker and therapeutic target.
Main Methods:
- Detected Nek2A mRNA and protein expression in breast cancer cell lines (MCF-10A, MCF-10DCIS.com, MCF-10CA1a) and human breast tissues (normal, DCIS, IDC).
- Correlated Nek2A expression with clinicopathological factors.
- Studied the effects of ectopic Nek2A expression and Nek2A knockdown on cell behavior.
Main Results:
- Nek2A mRNA and protein were significantly upregulated in breast cancer cell lines and tissues.
- Nek2A expression correlated with molecular subtypes, ER, PR, Ki-67, histological grade, and lymph node metastasis.
- Ectopic Nek2A expression caused abnormal centrosomes; Nek2A knockdown inhibited proliferation and induced cell cycle arrest.
Conclusions:
- Nek2A is closely associated with breast carcinoma development and progression.
- Nek2A may serve as a novel biomarker for breast cancer diagnosis.
- Nek2A represents a potential therapeutic target, particularly for ductal carcinoma in situ (DCIS).
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