Transducin-like enhancer of split 3 regulates proliferation of melanoma cells via histone deacetylase activity
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Masahiro Ogawa1,2, Tatsuki Yaginuma1, Chihiro Nakatomi1, Tsuyoshi Nakajima1, Yukiyo Tada-Shigeyama2, William N. Addison3, Mariko Urata1, Takuma Matsubara1, Koji Watanabe4, Kou Matsuo5, Tsuyoshi Sato6, Hiromi Honda7, Hisako Hikiji7, Seiji Watanabe2 and Shoichiro Kokabu1
1Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka, Japan
2Division of Dental Anesthesiology, Department of Science of Physical Functions, Kyushu Dental University, Kitakyushu, Fukuoka, Japan
3Research Unit, Shriners Hospitals for Children-Canada, Department of Human Genetics, McGill University, Montreal, Quebec, Canada
4Division of Developmental Stomatognathic Function Science, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka, Japan
5Division of Oral Pathology, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Fukuoka, Japan
6Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Saitama Medical University, Moroyama-machi, Iruma-gun, Saitama, Japan
7School of Oral Health Sciences, Kyushu Dental University, Kitakyushu, Fukuoka, Japan
Shoichiro Kokabu, email: firstname.lastname@example.org
Keywords: malignant melanoma; transcriptional co-repressor; trichostatin A; HDAC inhibitors
Received: August 12, 2018 Accepted: December 20, 2018 Published: January 08, 2019
Melanoma, one of the most aggressive neoplasms, is characterized by rapid cell proliferation. Transducin-like Enhancer of Split (TLE) is an important regulator of cell proliferation via Histone deacetylase (HDAC) recruitment. Given that HDAC activity is associated with melanoma progression, we examined the relationship between TLE3, a TLE family member, and melanoma. TLE3 expression was increased during the progression of human patient melanoma (p < 0.05). Overexpression of Tle3 in B16 murine melanoma cells led to an increase in cell proliferation (p < 0.01) as well as the number of cyclinD1-positive cells. in vivo injection of mice with B16 cells overexpressing Tle3 resulted in larger tumor formation than in mice injected with control cells (p < 0.05). In contrast, siRNA-mediated knockdown of Tle3 in B16 cells or TLE3 in HMV-II human melanoma cells decreased proliferation (p < 0.01). Treatment of B16 cells with trichostatin A (2.5 μM), a class I and II HDAC inhibitor, prevented the effect s of Tle3 on proliferation. In conclusion, these data indicate that Tle3 is required, at least in part, for proliferation in the B16 mouse melanoma model.
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