Digestive Diseases and Sciences

, Volume 61, Issue 2, pp 444–452 | Cite as

Keratinocyte Growth Factor Regulation of Aryl Hydrocarbon Receptor Activation in Colorectal Cancer Cells

  • Jiuheng Yin
  • Baifa Sheng
  • Aimin Pu
  • Bin Han
  • Kunqiu Yang
  • Qimeng Wang
  • Lihua Sun
  • Hua Yang
Original Article



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.


The aim of the present study was to explore a new role for AhR in KGF-induced colon cancer cell growth.

Materials and 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.


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.


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.


Aryl hydrocarbon receptor KGF Cyclin D1 Colorectal cancer cells 



This research was supported by grants from the National Natural Science Foundation of China (NSFC 81330013 to H.Y.) and the Program of Changjiang Scholars and Innovative Research (IRT 13050 to H.Y.).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jiuheng Yin
    • 1
  • Baifa Sheng
    • 1
  • Aimin Pu
    • 1
  • Bin Han
    • 1
  • Kunqiu Yang
    • 1
  • Qimeng Wang
    • 1
  • Lihua Sun
    • 1
  • Hua Yang
    • 1
  1. 1.Department of General Surgery, Xinqiao HospitalThird Military Medical UniversityChongqingChina

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