title: HOXB7 as a prognostic factor and mediator of colorectal cancer progression.
abstract: OBJECTIVE
  This study was to investigate the clinicopathologic significance and potential role of HOXB7 in the development and progression of colorectal cancer (CRC).
  
  
  METHODS
  The relationship between HOXB7 expression and clinical characteristics of CRC was analyzed in 224 paraffin-embedded archived CRC specimens by immunohistochemistry (IHC). The effects of HOXB7 on cell growth and proliferation, as well as on tumorigenesis, were examined both in vitro and in vivo, using MTT assay, colony formation assay, cell cycle analysis, soft agar assay, and tumorigenesis in nude mice. Western blotting and real-time reverse transcriptase-PCR were performed to examine the impact of HOXB7 on the PI3K/Akt and MAPK signaling pathways.
  
  
  RESULTS
  HOXB7 protein level was significantly correlated with advanced Dukes stage (P < 0.001), T stage (P = 0.012), distant metastasis (P = 0.042), higher proliferation index (P = 0.007) and poor survival of patients (P = 0.005). Enforced expression of HOXB7 in CRC cell lines significantly enhanced cell growth, proliferation and tumorigenesis. Conversely, knockdown of HOXB7 caused an inhibition of cell growth, proliferation, and tumorigenesis. We also showed that HOXB7 accelerated G(0)-G(1) to S-phase transition concomitantly with upregulation of cyclin D1 and downregulation of p27Kip1. On the contrary, knockdown of HOXB7 caused G(1)-S-phase arrest, downregulation of cyclin D1 and upregulation of p27Kip1. Enforced expression of HOXB7 could enhance PI3K/AKT and MAPK pathway activity.
  
  
  CONCLUSIONS
  Our findings suggest that HOXB7 protein, as a valuable marker of CRC prognosis, plays an important role in the development and progression of human CRC.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Liao
authors.forename: Dan
authors.initials: D
authors.lastname: Jiang
authors.forename: Jian
authors.initials: J
authors.lastname: Yuan
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Cui
authors.forename: Xi-Wen
authors.initials: XW
authors.lastname: Shi
authors.forename: Cui-Min
authors.initials: CM
authors.lastname: Chen
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Deng
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Ding
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; C490538:HOXB7 protein, human; D018398:Homeodomain Proteins