Nek2C functions as a tumor promoter in human breast tumorigenesis
Ziyu Liu1, Yahong Wang, Shuling Wang
1Department of Breast Cancer Pathology and Research Laboratory, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, PR China.
Abstract:
The serine⁄threonine kinase Nek2 has been proposed as a requirement for the progression of breast cancer. The aim of this study was to investigate the expression of Nek2C, which is a splice variant of Nek2, and the role it plays in the different stages of breast cancer. We investigated the role of Nek2C in the MCF10 breast cancer cell lines, MCF10A, MCF10AT, MCF10DCIS.com and MCF10CA1a, using RNA interference and plasmid transfection, as well as breast tissue samples of normal breast tissue (NBT), atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). We detected the mRNA Nek2C expression levels in the MCF10 cell lines and in human breast samples. Our results revealed that the mRNA expression of Nek2C was significantly upregulated in the MCF10DCIS.com and MCF10CA1a cell lines as well as in human primary breast cancer tissue (DCIS and IDC). As expected, the Nek2C downregulation, using RNA interference, decreased the survival, invasion and migration of MCF10DCIS.com and MCF10CA1a cells. Consistent with these results, the Nek2C upregulation in MCF10A and MCF10AT cells using plasmid transfection increased the survival ability of these cells. Our results also revealed a correlation between Nek2C mRNA expression levels and tumor grade. Taken together, our findings suggest that Nek2C plays a signicficant role in breast cancer development and that Nek2C inhibition may be a useful therapeutic approach to targeting human breast tumors.
Insights
The serine/threonine kinase Nek2C is upregulated in breast cancer, promoting tumor cell survival, invasion, and migration. Inhibiting Nek2C may offer a new therapeutic strategy for breast tumors.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The serine/threonine kinase Nek2 is implicated in breast cancer progression.
- Nek2C is a splice variant of Nek2 with a proposed role in cancer development.
Purpose of the Study:
- To investigate the expression of Nek2C in different stages of breast cancer.
- To elucidate the role of Nek2C in breast cancer cell survival, invasion, and migration.
Main Methods:
- Analysis of Nek2C mRNA expression in MCF10 breast cancer cell lines (MCF10A, MCF10AT, MCF10DCIS.com, MCF10CA1a) and human breast tissue samples (NBT, ADH, DCIS, IDC).
- Utilized RNA interference for Nek2C downregulation and plasmid transfection for Nek2C upregulation.
- Correlated Nek2C expression levels with tumor grade.
Main Results:
- Nek2C mRNA expression was significantly upregulated in advanced breast cancer cell lines (MCF10DCIS.com, MCF10CA1a) and primary breast cancer tissues (DCIS, IDC).
- Downregulation of Nek2C reduced survival, invasion, and migration of cancer cells.
- Upregulation of Nek2C enhanced survival in non-malignant/less malignant cell lines.
Conclusions:
- Nek2C plays a significant role in breast cancer development and progression.
- Nek2C expression correlates with tumor grade.
- Targeting Nek2C could be a potential therapeutic strategy for breast tumors.
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