三阴性乳腺癌是一类肿瘤分化程度低、异质性高、复发转移率高的肿瘤，因缺乏有效的治疗靶点而成为乳腺癌的治疗难题。LNK是我们采用基因芯片筛选三阴性乳腺癌与非三阴性乳腺癌组织中差异表达基因时发现、低表达于三阴性乳腺癌的基因。前期研究发现，LNK在三阴性乳腺癌细胞MDA-MB-231中过表达可抑制其增殖能力；LNK基因敲除小鼠乳管内注射RCAS其乳腺上皮增生活跃；LNK过表达后p-JAK2表达下调,初步确定LNK调控JAK2信号通路。本研究拟取受体表达状态不同的乳腺癌细胞，采用过表达、沉默策略，从细胞行为及分子特征方面，明确LNK在三阴性乳腺癌增殖过程中的功能；通过LNK基因敲除小鼠诱导三阴性乳腺癌，明确LNK在三阴性乳腺癌发生发展中的功能；以JAK2-STAT3为机制研究切入点，揭示LNK可能的作用机制。本研究具有源头创新性，将有助于理解三阴性乳腺癌发生发展的分子机制，为其靶向治疗提供新的靶点。

Due to the characters of low degree of differentiation, high heterogeneity, serious metastasis ability, high recurrence frequency, and importantly the ineffective therapeutic target, triple-negative breast cancer(TNBC) becomes one difficult trouble of breast cancer clinical treatment. LNK is significantly down-regulated in TNBC, identified from differential gene expression profile between TNBC tissue and non-TNBC tissue. Previous study showed that over-expression of LNK in TNBC cells could inhibit the growth ability; infection of mammary glands of LNK knockout mouse with retrovirus (replication-competent avian sarcoma-leukosis virus, RCAS) vector, the mammary epithelial cells are more proliferation; p-JAK2 is down-regulated via LNK overexpression, which indicate that JAK2 might be the singnaling pathway by LNK regulated. This study will confirm the role of LNK, using overexpression and knock down strategies in the breast cancer cells which differentially express ER, PR, or Her-2, playing in the TNBC proliferation progression by analyzing the cell behavior and molecular characteristics; we will also use RCAS into mammary glands of LNK knockout mouse initiating carcinogenesis to evaluating the effect of LNK on TNBC cells growth; subsequently clarify the underlying mechanism between LNK and JAK2-STAT3. Up to now, there was no report about the function and mechanism of LNK in regulating the TNBC growth progression. The innovative proposal by this study could possibly find a new target for the targeted therapeutics of TNBC.