re-expression of akap12 inhibits progression and metastasis potential of colorectal carcinoma in vivo and in vitro表达akap12抑制大肠癌癌的进展和转移潜力的体内和体外.pdfVIP

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re-expression of akap12 inhibits progression and metastasis potential of colorectal carcinoma in vivo and in vitro表达akap12抑制大肠癌癌的进展和转移潜力的体内和体外.pdf

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re-expression of akap12 inhibits progression and metastasis potential of colorectal carcinoma in vivo and in vitro表达akap12抑制大肠癌癌的进展和转移潜力的体内和体外

Re-Expression of AKAP12 Inhibits Progression and Metastasis Potential of Colorectal Carcinoma In Vivo and In Vitro 1 1,2 1 2 1 Weiwei Liu *, Ming Guan , Tingting Hu , Xiaoye Gu , Yuan Lu * 1 Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China, 2 Central Laboratory, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China Abstract Background: AKAP12/Gravin (A kinase anchor protein 12) is one of the A-kinase scaffold proteins and a potential tumor suppressor gene in human primary cancers. Our recent study demonstrated the highly recurrent loss of AKAP12 in colorectal cancer and AKAP12 reexpression inhibited proliferation and anchorage-independent growth in colorectal cancer cells, implicating AKAP12 in colorectal cancer pathogenesis. Methods: To evaluate the effect of this gene on the progression and metastasis of colorectal cancer, we examined the impact of overexpressing AKAP12 in the AKAP12-negative human colorectal cancer cell line LoVo, the single clone (LoVo- AKAP12) compared to mock-transfected cells (LoVo-CON). Results: pCMV6-AKAP12-mediated AKAP12 re-expression induced apoptosis (3% to 12.7%, p ,0.01), migration (89.6 67.5 cells to 31.0 64.1 cells, p ,0.01) and invasion (82.7 65.2 cells to 24.763.3 cells, p ,0.01) of LoVo cells in vitro compared to control cells. Nude mice injected with LoVo-AKAP12 cells had both significantly reduced tumor volume (p ,0.01) and increased apoptosis compared to mice given AKAP12-CON. The quantitative human-specific Alu PCR analysis showed overexpression of AKAP12 suppressed the number of intravasated cells in vivo (p