Abstract
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.
Highlights
Malignant melanoma is one of the most aggressive neoplasms
Given that Histone deacetylase (HDAC) activity is associated with melanoma progression, we examined the relationship between TLE3, a Transducin-like Enhancer of Split (TLE) family member, and melanoma
The expression of TLE3 was further increased in malignant samples compared to benign skin nevi (Figure 1A), suggesting that the expression of TLE3 is involved in the progression of melanoma
Summary
Malignant melanoma is one of the most aggressive neoplasms. The worldwide incidence of melanoma has been steadily increasing with mortality rates rising faster than any other form of cancer [1]. Major advancements have been achieved for metastatic melanomas via the blockade of immune-checkpoints using a programmed death 1 (PD-1) checkpoint inhibitor and a cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) checkpoint inhibitor [3]. These drugs may cause adverse immune-related events such as interstitial www.oncotarget.com pneumonia, large intestine inflammation, and type I diabetes [4]. Primary non-response as well as acquired resistance to immune-checkpoint blockers remain a challenge. The need for the development of novel treatment approaches remain
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