Estrogen receptor alpha variant ERalpha46 mediates growth inhibition and apoptosis of human HT-29 colon adenocarcinoma cells in the presence of 17beta-oestradiol.
BACKGROUND
Estrogen is involved in suppression of colon cancer development and exerts its function via estrogen receptors alpha and beta (ERalpha, ERbeta). The recently identified ERalpha46 resulted from exon 1-deletion from the 66-kDa full length form of ERalpha66 is devoid of the transactivation domain AF-1, whose function remains largely unknown.


METHODS
In this study, we compared the expression of ERalpha46 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 ERalpha46, was transfected with ERalpha46-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 17beta-oestradiol.


RESULTS
Higher ERalpha46 mRNA levels were observed in normal colorectal tissues than in the corresponding cancer tissues. ERalpha46-transfected cells showed a significantly decreased growth rate than control cells and an accumulation of cells in the G(0/1) phase and a reduced proportion of cells in G(2)/M phase after exposed to 10(-8) mol/L 17beta-oestradiol. There were also more positive TUNEL stained cells in ERalpha46-transfected cells than the control cells in the presence of 17beta-oestradiol (P < 0.05).


CONCLUSIONS
These data suggest that ERalpha46 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 17beta-oestradiol.
Jiang
Hai-ping
HP
Department of Oncological Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Teng
Rong-yue
RY
Wang
Qi
Q
Zhang
Xing
X
Wang
Hao-hao
HH
Cao
Jiang
J
Teng
Li-song
LS
D000328:Adult; D000368:Aged; D017209:Apoptosis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D016193:G1 Phase; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D004958:Estradiol