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https://doi.org/10.1038/s41419-018-1177-6
Title: | Expression of two non-mutated genetic elements is sufficient to stimulate oncogenic transformation of human mammary epithelial cells | Authors: | Pandey, V Zhang, M You, M Zhang, W Chen, R Zhang, W Ma, L Wu, Z.-S Zhu, T Xu, X.Q Lobie, P.E |
Keywords: | cyclin D1 doxorubicin protein bcl 2 small interfering RNA STAT3 protein trefoil factor 3 acinar cell anchorage independent growth animal experiment animal model Article breast carcinoma breast epithelium cell carcinogenesis carcinogenicity cell proliferation cell survival cell viability cohort analysis controlled study gene expression HMEC-hTERT cell line human human cell immortalized cell line immune deficiency major clinical study MCF-10AT cell line MCF-12A cell line mouse nonhuman oncogene phenotype priority journal protein expression protein function regulatory mechanism transcription regulation upregulation |
Issue Date: | 2018 | Publisher: | Nature Publishing Group | Citation: | Pandey, V, Zhang, M, You, M, Zhang, W, Chen, R, Zhang, W, Ma, L, Wu, Z.-S, Zhu, T, Xu, X.Q, Lobie, P.E (2018). Expression of two non-mutated genetic elements is sufficient to stimulate oncogenic transformation of human mammary epithelial cells. Cell Death and Disease 9 (12) : 1147. ScholarBank@NUS Repository. https://doi.org/10.1038/s41419-018-1177-6 | 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. © 2018, The Author(s). | Source Title: | Cell Death and Disease | URI: | https://scholarbank.nus.edu.sg/handle/10635/174191 | ISSN: | 2041-4889 | DOI: | 10.1038/s41419-018-1177-6 |
Appears in Collections: | Elements Staff Publications |
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