title: Re-expression of AKAP12 inhibits progression and metastasis potential of colorectal carcinoma in vivo and in vitro.
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±7.5 cells to 31.0±4.1 cells, p<0.01) and invasion (82.7±5.2 cells to 24.7±3.3 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<0.01).
  
  
  CONCLUSIONS
  These results demonstrate that AKAP12 may play an important role in tumor growth suppression and the survival of human colorectal cancer.
authors.affiliation: Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China. yuanlu@hsh.stn.sh.cn
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Guan
authors.forename: Tingting
authors.initials: T
authors.lastname: Hu
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Gu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D018797:Cell Cycle Proteins