Background Estrogen is involved in suppression of colon cancer development and exerts its function via estrogen receptors α and β （ERa, ERβ）. The recently identified ERα46 resulted from exon 1-deletion from the ...Background Estrogen is involved in suppression of colon cancer development and exerts its function via estrogen receptors α and β （ERa, ERβ）. The recently identified ERα46 resulted from exon 1-deletion from the 66-kDa full length form of ERa66 is devoid of the transactivation domain AF-1, whose function remains largely unknown. Methods In this study, we compared the expression of ERa46 mRNA in 32 normal colorectal tissues and their matched colorectal cancer tissues by real-time quantitative polymerase chain reaction （PCR）. Human colon adenocarcinoma cell HT-29, that has low endogenous expression of ERα46, was transfected with ERα46-expression vector; methyl thiazolyl tetrazolium （MTT） assay, flow cytometry, DNA fragmentation and TUNEL staining were used to evaluate the proliferation and apoptosis status of the cells in the presence of 17β-oestradiol. Results Higher ERα46 mRNA levels were observed in normal colorectal tissues than in the corresponding cancer tissues. ERα46-transfected cells showed a significantly decreased growth rate than control cells and an accumulation of cells in the G0/1 phase and a reduced proportion of cells in G2/M phase after exposed to 10^-8 mol/L 17β-oestradiol. There were also more positive TUNEL stained cells in ERα46-transfected cells than the control cells in the presence of 17β-oestradiol （P 〈0.05）. Conclusions These data suggest that ERα46 may be involved in the development and/or progression of colorectal cancer via mediating growth inhibition and apoptosis of cancer cells in the presence of 17β-oestradiol.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30772510）, Ministry Health of the People＇s Republic of China （No. WKJ2006-2-008）, and Department of Science and Technology of Zhejiang Province （No. 2007C24011）.
文摘Background Estrogen is involved in suppression of colon cancer development and exerts its function via estrogen receptors α and β （ERa, ERβ）. The recently identified ERα46 resulted from exon 1-deletion from the 66-kDa full length form of ERa66 is devoid of the transactivation domain AF-1, whose function remains largely unknown. Methods In this study, we compared the expression of ERa46 mRNA in 32 normal colorectal tissues and their matched colorectal cancer tissues by real-time quantitative polymerase chain reaction （PCR）. Human colon adenocarcinoma cell HT-29, that has low endogenous expression of ERα46, was transfected with ERα46-expression vector; methyl thiazolyl tetrazolium （MTT） assay, flow cytometry, DNA fragmentation and TUNEL staining were used to evaluate the proliferation and apoptosis status of the cells in the presence of 17β-oestradiol. Results Higher ERα46 mRNA levels were observed in normal colorectal tissues than in the corresponding cancer tissues. ERα46-transfected cells showed a significantly decreased growth rate than control cells and an accumulation of cells in the G0/1 phase and a reduced proportion of cells in G2/M phase after exposed to 10^-8 mol/L 17β-oestradiol. There were also more positive TUNEL stained cells in ERα46-transfected cells than the control cells in the presence of 17β-oestradiol （P 〈0.05）. Conclusions These data suggest that ERα46 may be involved in the development and/or progression of colorectal cancer via mediating growth inhibition and apoptosis of cancer cells in the presence of 17β-oestradiol.
