Breast cancer is the most common solid tumor and the second most common cause of death in women. Despite a large body of literature and progress in breast cancer research, many molecular aspects of this complex disease are still poorly understood, hindering the design of specific and effective therapeutic strategies. To identify molecules important in breast cancer progression and metastasis, we tested the in vivo effects of inhibiting the functions of various kinases and genes involved in the regulation/modulation of the cytoskeleton by downregulating them in mouse PyMT mammary tumor cells and human breast cancer cell lines. These kinases and cytoskeletal regulators were selected based on their prognostic values for breast cancer patient survival. PyMT tumor cells in which a selected gene was stably knocked down were injected into the tail veins of mice and the formation of tumors in the lungs was monitored. One of several genes found to be important for tumor growth in lungs was Nek2, a cell cycle-related protein kinase. Furthermore, Nek2 was also important for tumor growth in the mammary fat pad.In various human breast cancer cell lines, Nek2 knockdown induced aneuploidy and cell cycle arrest that led to cell death. Significantly, the breast cancer cell line most sensitive to Nek2 depletion was of the triple negative breast cancer subtype. Our data indicate that Nek2 plays a pivotal role in breast cancer growth at primary and secondary sites, and thus may be an attractive and novel therapeutic target for this disease.
ACC of the breast has a relatively prolonged natural history, and responds well to conservative management at presentation, with good outcome, even following local recurrence.
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