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• W2900562716 abstract "Abstract Trefoil factor 3 (TFF3) expression is positively associated with advanced clinicopathological features of mammary carcinoma (MC). Herein, we provide evidence for a functional role of TFF3 in oncogenic transformation of immortalized , but otherwise normal human mammary epithelial cells (HMECs), namely, HMEC- hTERT , MCF10A, and MCF12A. Forced expression of TFF3 in immortalized -HMECs enhanced cell proliferation, cell survival, anchorage-independent growth, produced highly disorganised three-dimensional (3D) acinar structures and generated tumours in immunocompromised mice. Forced expression of TFF3 in immortalized -HMECs stimulated STAT3 activity that was required for TFF3-stimulated cell proliferation, survival, and anchorage-independent growth. TFF3 specifically utilised STAT3 activity to govern a transcriptional program, which was required for TFF3-stimulated oncogenic transformation of immortalized -HMECs, including transcriptional upregulation of CCND1 and BCL2 . siRNA -mediated depletion or functional inhibition of STAT3 significantly inhibited the TFF3-stimulated transcription of CCND1 and BCL2 and oncogenicity in immortalized -HMECs. Furthermore, DOX-inducible expression of TFF3 in HMEC- hTERT cells also permitted anchorage-independent growth and produced disorganized acinar structures in 3D Matrigel culture. Removal of DOX-induced expression of TFF3 in HMEC- hTERT cells, previously grown with DOX, resulted in efficient normalisation of the disorganized acinar architecture and attenuated cell viability in Matrigel culture. Cumulatively, these findings suggest that TFF3 is a potent oncogene and its increased expression along with hTERT in HMECs is sufficient to produce oncogenic transformation." @default.
• W2900562716 created "2018-11-29" @default.
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• W2900562716 date "2018-11-19" @default.
• W2900562716 modified "2023-10-12" @default.
• W2900562716 title "Expression of two non-mutated genetic elements is sufficient to stimulate oncogenic transformation of human mammary epithelial cells" @default.
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• W2900562716 doi "https://doi.org/10.1038/s41419-018-1177-6" @default.
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