Jiuheng Yin1, Baifa Sheng1, Aimin Pu1, Bin Han1, Kunqiu Yang1, Qimeng Wang1, Lihua Sun1, Hua Yang2. 1. Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. 2. Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. huayang@tmmu.edu.cn.
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. AIM: 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. 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.
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. AIM: 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. 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.
Entities:
Keywords:
Aryl hydrocarbon receptor; Colorectal cancer cells; Cyclin D1; KGF
Authors: B D Abbott; J E Schmid; J A Pitt; A R Buckalew; C R Wood; G A Held; J J Diliberto Journal: Toxicol Appl Pharmacol Date: 1999-02-15 Impact factor: 4.219
Authors: Martina Karasová; Jiřina Procházková; Zuzana Tylichová; Radek Fedr; Miroslav Ciganek; Miroslav Machala; Zdeněk Dvořák; Barbora Vyhlídalová; Iveta Zůvalová; Jiří Ehrmann; Jan Bouchal; Zdeněk Andrysík; Jan Vondráček Journal: Cancers (Basel) Date: 2022-08-31 Impact factor: 6.575