Research Papers:

Transducin-like enhancer of split 3 regulates proliferation of melanoma cells via histone deacetylase activity

Masahiro Ogawa, Tatsuki Yaginuma, Chihiro Nakatomi, Tsuyoshi Nakajima, Yukiyo Tada-Shigeyama, William N. Addison, Mariko Urata, Takuma Matsubara, Koji Watanabe, Kou Matsuo, Tsuyoshi Sato, Hiromi Honda, Hisako Hikiji, Seiji Watanabe and Shoichiro Kokabu _

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Oncotarget. 2019; 10:404-414. https://doi.org/10.18632/oncotarget.26552

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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

Correspondence to:

Shoichiro Kokabu, email: [email protected]

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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