| Background:Worldwide, breast cancer is the most common invasive cancer in women. In recentyears, the breast cancer incidence rates significantly increase. With the development ofevidence-based medicine and molecular biology, the systemic treatment has become theprimary means of breast cancer treatment. Although the development of endocrine andmolecular targeted therapy improves survival rate for patients with breast cancer，mostpatients die as a result of therapy resistance and abnormal proliferation or metastasis ofbreast cancer cells.So, finding new effective therapeutic targets and prognostic factors isimportant to the early diagnosis and therapy of breast cancer.The14-3-3family is highly conserved proteins of28-33KD. Proteins of this familyhave been found in all eukaryotic organisms studied so far. They received their name in1967during a systematic classification of brain proteins that was based on their fraction number on anion-exchange chromatography and migration position in gel electrophoresis.There are seven isoforms in mammals (β,ε,γ,η,σ,θ,ζ,) that show a considerable degreeof conservation of both structure and function. These14-3-3θregulated cellular processesinclude intracellular signal transduction, transcription, apoptosis, cell cycle control, cellmetabolism and so on. However, researchs about14-3-3θare limited, the expression of14-3-3θin breast cancer and the role of14-3-3θin the occurrence and development ofbreast cancer remains poorly understood. Are the clinicopathologic features relative to theexpression of14-3-3θprotein in breast cancer? Whether down-regulating the expressionsof14-3-3θprotein by si14-3-3θhas an impact on the malignant biological behavior ofbreast cancer cells is unknown. Can14-3-3θprotein be a new therapeutic target? In ourresearch, we investigate the expressions of14-3-3θprotein in breast cancer and itscorrelations with prognosis and the impact on the malignant biological behavior of breastcancer cells.Objective:To investigate the expression of14-3-3θprotein in an additional matched tumorand normal tissues; To investigate the expression of14-3-3θprotein in breast cancerpatients and its correlations with clinicopathological features,disease-free survival andoverall survival. The changes of the proliferation,invasiveness and migration capability ofthe breast cancer cells were evaluated after the14-3-3θexpression was downregulated bysi14-3-3θ.Methods:An additional33matched tumor and normal tissues were tested for differentialexpression of14-3-3θby immunohistochemistry and western-Blot. In216breast cancerpatients14-3-3θlevels were determined by immunohistochemistry and correlations of14-3-3θexpression with tumor clinicopathologic features, disease-free survival, andoverall survival of the patients were analyzed. Si14-3-3θwas introduced into humanbreast cancer cells, Western-Blot was employed to detect the expression of14-3-3θ protein in MDA-MB-231cells. MTT assay，wound healing assay and transwell chambermodels in vitro were used to detect the proliferation, mobility and invasiveness capabilityof cells.Result:Significant increased expression of14-3-3θwas detected in breast cancer specimenscompared with adjacent normal tissues. Increased14-3-3θexpression was correlated withadvanced TNM stage (P <0.05), lymph node metastasis (P <0.05), and ER negativestatus (P <0.05). The expression of14-3-3θprotein in MDA-MB-231/si14-3-3θcellswas much lower than the control groups(P<0.05).The proliferation，mobility andinvasiveness capability of the MDA-MB-231/si14-3-3θcells were much lower than thecontrol groups.Conclusion:The expression of14-3-3θin breast cancer specimens and adjacent normal tissueswas difference. It meant that14-3-3θprotein was relative to the occurrence of breastcancer. High14-3-3θexpression was associated with advanced TNM stage, lymph nodemetastasis and ER in breast cancer. It showed that14-3-3θprotein was relative to thedevelopment of breast cancer and it might be a powerful predictor of breast cancer.Transfection with si14-3-3θcould inhibit the expression of14-3-3θprotein. And theproliferation, mobility and invasiveness capability of the MDA-MB-231/si14-3-3θcellswere dereased. It predicted that14-3-3θmight be a potential therapeutic target in themolecular therapy. |
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