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Overexpression of TFF3 is involved in prostate carcinogenesis via blocking mitochondria-mediated apoptosis.

ABSTRACT: The overexpression of trefoil factor family 3 (TFF3) is observed in a variety of cancers, including prostate cancer (PCa), and its potential role in carcinogenesis, such as activating the PI3K/AKT pathway, is suggested. However, its role and its related mechanisms in prostate tumorigenesis remain unknown. To elucidate the role of TFF3 overexpression in PCa, we silenced TFF3 in two PCa cell lines that overexpressed TFF3 and explored the molecular mechanism behind its antiapoptotic role. We also examined TFF3 expression in 108 Korean PCa specimens and 106 normal prostate tissues by immunohistochemistry (IHC) analysis. The mean TFF3 IHC score in the tumor tissues was significantly higher than that in the normal tissues (4.702 vs. 0.311, P?=?2.52?×?10-24). TFF3-silenced cells showed suppressed tumor cell growth and migration. TFF3 silencing decreased BCL2 and increased BAX expression. The translocation of BAX to the mitochondria was also confirmed. After TFF3 silencing, the expression of the mitochondrial proapoptotic proteins, cytochrome C and Smac/DIABLO, was elevated, and these proteins were released from the mitochondria to the cytosol. Downstream mediators of mitochondrial apoptosis, including cleaved caspase-3, caspase-9, and PARP, were also elevated. Accordingly, the proportion of apoptotic cells was significantly higher among TFF3-silenced cells. There was no difference in extrinsic apoptosis-related molecules after TFF3 silencing. All the results support that TFF3 silencing induces the downstream signaling pathway of mitochondria-mediated apoptosis. This study provides a better understanding of the mechanism of prostate tumorigenesis, suggesting TFF3 as a potential biomarker and therapeutic target of PCa.

SUBMITTER: Liu J

PROVIDER: S-EPMC6107499 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Overexpression of TFF3 is involved in prostate carcinogenesis via blocking mitochondria-mediated apoptosis.

Liu Jieying J Kim So Youn SY Shin Sun S Jung Seung-Hyun SH Yim Seon-Hee SH Lee Ji Youl JY Lee Sug-Hyung SH Chung Yeun-Jun YJ

Experimental & molecular medicine 20180823 8

The overexpression of trefoil factor family 3 (TFF3) is observed in a variety of cancers, including prostate cancer (PCa), and its potential role in carcinogenesis, such as activating the PI3K/AKT pathway, is suggested. However, its role and its related mechanisms in prostate tumorigenesis remain unknown. To elucidate the role of TFF3 overexpression in PCa, we silenced TFF3 in two PCa cell lines that overexpressed TFF3 and explored the molecular mechanism behind its antiapoptotic role. We also e ...[more]

PMID: 30139961

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Overexpression of TFF3 is involved in prostate carcinogenesis via blocking mitochondria-mediated apoptosis.

Publications

Overexpression of TFF3 is involved in prostate carcinogenesis via blocking mitochondria-mediated apoptosis.

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