Gene Expression Profiling for Plk2 -/- mammary gland

Identify gene expression changes in the absence of Plk2 Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and is a putative tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development and as a tumor suppressor in mammary tumorigenesis. Disruptions in polarity and mitotic spindle orientation contribute to the progression and evolution of tumorigenesis. However, little is known about the molecular mechanisms regulating these processes in vivo. Here we demonstrate that Polo-like kinase 2 (Plk2) regulates mitotic spindle orientation in the mammary gland and is a putative tumor suppressor. Plk2 is highly expressed in the mammary gland and is required for proper mammary gland development. Loss of Plk2 leads to increased mammary epithelial cell proliferation and ductal hyperbranching. Additionally a novel role for Plk2 in regulating the orientation of the mitotic spindle and maintaining proper cell polarity in the ductal epithelium was discovered. In support of a tumor suppressor function for Plk2, loss of Plk2 increased the formation of lesions in multiparous glands. Collectively, these results demonstrate a novel role for Plk2 in regulating mammary gland development and as a tumor suppressor in mammary tumorigenesis. Comparison between Plk2 +/+ (n=3) and Plk2 -/- (n=3) mouse mammary epithelial cells本研究旨在鉴定Plk2缺失条件下的基因表达变化。细胞极性与有丝分裂纺锤体定向紊乱可促进肿瘤发生的进程与演进。然而，目前对于体内调控此类过程的分子机制仍所知甚少。本研究证实，Polo样激酶2（Polo-like kinase 2，Plk2）可调控乳腺组织中的有丝分裂纺锤体定向，是一种潜在的肿瘤抑制因子。Plk2在乳腺中高表达，且对正常乳腺发育不可或缺。Plk2缺失会导致乳腺上皮细胞增殖增强及导管过度分支。此外，本研究还发现了Plk2的全新功能：其可调控导管上皮细胞的有丝分裂纺锤体定向，并维持正常的细胞极性。为验证Plk2的肿瘤抑制功能，研究发现Plk2缺失会增加经产小鼠乳腺病变灶的形成。综上，本研究结果揭示了Plk2在调控乳腺发育中的全新功能，以及其在乳腺肿瘤发生中作为肿瘤抑制因子的作用。 细胞极性与有丝分裂纺锤体定向紊乱可促进肿瘤发生的进程与演进。然而，目前对于体内调控此类过程的分子机制仍所知甚少。本研究证实，Polo样激酶2（Polo-like kinase 2，Plk2）可调控乳腺组织中的有丝分裂纺锤体定向，是一种潜在的肿瘤抑制因子。Plk2在乳腺中高表达，且对正常乳腺发育不可或缺。Plk2缺失会导致乳腺上皮细胞增殖增强及导管过度分支。此外，本研究还发现了Plk2的全新功能：其可调控导管上皮细胞的有丝分裂纺锤体定向，并维持正常的细胞极性。为验证Plk2的肿瘤抑制功能，研究发现Plk2缺失会增加经产小鼠乳腺病变灶的形成。综上，本研究结果揭示了Plk2在调控乳腺发育中的全新功能，以及其在乳腺肿瘤发生中作为肿瘤抑制因子的作用。 本研究对Plk2野生型（Plk2 +/+，n=3）与Plk2敲除型（Plk2 -/-，n=3）小鼠乳腺上皮细胞进行了比较。