Nek2A contributes to tumorigenic growth and possibly functions as potential therapeutic target for human breast cancer.

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.

• Authors: Shuling Wang, Weidong Li, Ning Liu, Fei Zhang, Han Liu, Fen Liu, Junjun Liu, Tongxian Zhang, Yun Niu
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 113 Issue 6 Pg. 1904-14 (Jun 2012) ISSN: 1097-4644 [Electronic] United States
• PMID: 22234886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Biomarkers, Tumor
• Ki-67 Antigen
• RNA, Messenger
• RNA, Small Interfering
• Receptors, Estrogen
• Receptors, Progesterone
• NEK2 protein, human
• NIMA-Related Kinases
• Protein Serine-Threonine Kinases

Topics

• Biomarkers, Tumor
• Breast Neoplasms (genetics, metabolism, pathology)
• Carcinoma, Ductal, Breast (genetics, metabolism, pathology)
• Carcinoma, Intraductal, Noninfiltrating (genetics, metabolism, pathology)
• Cell Cycle Checkpoints (genetics)
• Cell Differentiation (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Disease Progression
• Female
• Gene Expression Profiling
• Humans
• Ki-67 Antigen (genetics)
• NIMA-Related Kinases
• Protein Serine-Threonine Kinases (biosynthesis, genetics, physiology)
• RNA Interference
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering
• Receptors, Estrogen (genetics)
• Receptors, Progesterone (genetics)