title: Keratinocyte Growth Factor Regulation of Aryl Hydrocarbon Receptor Activation in Colorectal Cancer Cells.
abstract: BACKGROUND
  Keratinocyte growth factor (KGF) stimulates normal growth, development and intestinal epithelial cell proliferation. Cyclin D1 promotes the cell cycle by inhibiting retinoblastoma protein (RB1). The activated aryl hydrocarbon receptor (AhR) has an important influence on the development of tumors through its interactions with the cell cycle.
  
  
  OBJECTIVE
  The aim of the present study was to explore a new role for AhR in KGF-induced colon cancer cell growth.
  
  
  METHODS
  Real-time PCR, western blot or immunofluorescence analysis were used to detect the expression of KGF, AhR, cyclin D1 and CYP1A1. Immunohistochemistry was used to observe the localization of AhR. MTT assay and flow cytometric analyses were performed to measure cell viability and the cell cycle.
  
  
  RESULTS
  Real-time PCR analysis revealed that KGF, AhR, and CYP1A1 mRNAs were overexpressed in colorectal cancer tissues. Meanwhile, overexpression of AhR was primarily observed in epithelial cells. In in vitro assay, KGF promoted colon cancer cell growth, as well as up-regulated and activated AhR. At the same time, AhR-knockdown colon cancer cells were less responsive to KGF. Western blot analysis, real-time PCR, or immunofluorescence data indicated that cyclin D1 expression was up-regulated by KGF but this up-regulation was compromised when AhR was silenced, and the cell cycle was arrested in the G0/G1 stage in these cells.
  
  
  CONCLUSIONS
  Our study suggests that KGF, AhR, and CYP1A1 are overexpressed in colorectal cancer tissues. Moreover, we reveal a new mechanism by which KGF promotes cell proliferation through the AhR-cyclin D1 pathway in colon cancer cells.
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Jiuheng
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Baifa
authors.initials: B
authors.lastname: Sheng
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Pu
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Kunqiu
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Qimeng
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. huayang@tmmu.edu.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
mesh_terms: D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D051523:Fibroblast Growth Factor 7 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*
chemical_list: C530104:CCND1 protein, human; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D051523:Fibroblast Growth Factor 7; D019938:Cyclin D1; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1
keywords: Aryl hydrocarbon receptor; Colorectal cancer cells; Cyclin D1; KGF