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Title: Hypomethylation associated enhanced transcription of trefoil factor-3 mediates tamoxifen-stimulated oncogenicity of ER+ endometrial carcinoma cells
Authors: Pandey, V 
Zhang, M
Chong, Q.-Y 
You, M 
Raquib, A.R 
Pandey, A.K 
Liu, D.-X
Liu, L
Ma, L
Jha, S 
Wu, Z.-S
Zhu, T
Lobie, P.E 
Keywords: caspase 7
cyclin D1
cyclin dependent kinase 2
cyclin dependent kinase 4
cyclin dependent kinase inhibitor 1B
estrogen receptor alpha
Ki 67 antigen
messenger RNA
protein bcl 2
protein c jun
protein p53
scatter factor receptor
STAT3 protein
transcription factor Snail
transcription factor Sp1
trefoil factor 3
Twist related protein 1
AN3-CA cell line
anchorage independent growth
animal cell
animal experiment
animal model
animal tissue
BCL2 gene
BCL2L1 gene
CASP7 gene
CCND1 gene
CCNE1 gene
CDK2 gene
CDK4 gene
CDKN1B gene
cell cycle progression
cell cycle S phase
cell migration
cell proliferation
cell survival
cell viability
clinical article
cohort analysis
controlled study
DNA methylation
ECC-1 cell line
endometrial carcinoma cell line
endometrium carcinoma
FN1 gene
gene expression regulation
human cell
human tissue
marker gene
OCLN gene
promoter region
protein expression
RL95-2 cell line
TFF3 gene
transcription initiation
tumor growth
tumor invasion
tumor suppressor gene
tumor volume
tumor xenograft
TWIST1 gene
VIM gene
Issue Date: 2017
Citation: Pandey, V, Zhang, M, Chong, Q.-Y, You, M, Raquib, A.R, Pandey, A.K, Liu, D.-X, Liu, L, Ma, L, Jha, S, Wu, Z.-S, Zhu, T, Lobie, P.E (2017). Hypomethylation associated enhanced transcription of trefoil factor-3 mediates tamoxifen-stimulated oncogenicity of ER+ endometrial carcinoma cells. Oncotarget 8 (44) : 77268-77291. ScholarBank@NUS Repository.
Abstract: Tamoxifen (TAM) is widely used as an adjuvant therapy for women with breast cancer (BC). However, TAM possesses partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial carcinoma (EC). The molecular mechanism for these observations is not well understood. Herein, we demonstrated that forced expression of Trefoil factor 3 (TFF3), in oestrogen receptorpositive (ER+) EC cells significantly increased cell cycle progression, cell survival, anchorage-independent growth, invasiveness and tumour growth in xenograft models. Clinically, elevated TFF3 protein expression was observed in EC compared with normal endometrial tissue, and its increased expression in EC was significantly associated with myometrial invasion. TAM exposure increased expression of TFF3 in ER+ EC cells and its elevated expression resulted in increased oncogenicity and invasiveness. TAM-stimulated expression of TFF3 in EC cells was associated with hypomethylation of the TFF3 promoter sequence and c-JUN/SP1-dependent transcriptional activation. In addition, small interfering (si) RNA-mediated depletion or polyclonal antibody inhibition of TFF3 significantly abrogated oncogenicity and invasiveness in EC cells consequent to TAM induction or forced expression of TFF3. Hence, TAM-stimulated upregulation of TFF3 in EC cells was critical in promoting EC progression associated with TAM treatment. Importantly, inhibition of TFF3 function might be an attractive molecular modality to abrogate the stimulatory effects of TAM on endometrial tissue and to limit the progression of EC. © Pandey et al.
Source Title: Oncotarget
ISSN: 19492553
DOI: 10.18632/oncotarget.20461
Appears in Collections:Staff Publications

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