Down-regulation of the expression of O-acetyl-GD3 by the O-acetylesterase cDNA in hamster melanoma cells:: Effects on cellular proliferation, differentiation, and melanogenesis
Down-regulation of the expression of O-acetyl-GD3 by the O-acetylesterase cDNA in hamster melanoma cells:: Effects on cellular proliferation, differentiation, and melanogenesis
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DOI：
10.1046/j.1471-4159.1999.0720954.x
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发表时间：
1999-03-01
影响因子：
4.7
通讯作者：
Yu, RK
中科院分区：
文献类型：
--
作者：
Birklé, S;Ren, SL;Yu, RK
仓鼠黑色素瘤细胞神经节苷脂的组成与其细胞生长和分化程度密切相关，生长缓慢、高度分化的黑色素瘤MI细胞表达GM3，而生长快速、未分化的Ab黑色素瘤细胞则以GD3和O-乙酰-GD3为主。为了研究 O-乙酰基-GD3 的假定功能，我们用丙型流感病毒的 O-乙酰酯酶基因建立了稳定转染的 AbC-1 无色仓鼠黑色素瘤细胞，以水解 O-乙酰基-GD3 中的 O-乙酰基。转染表达O-乙酰酯酶基因的细胞中O-乙酰-GD3含量降低>90%。这些 O-乙酰基-GD3 耗尽的细胞在细胞形态、生长行为和黑素生成活性方面与亲本细胞不同。转染细胞中缺乏O-乙酰基-GD3，伴随着厚树突形成增加和细胞体增大，这与圆形和扁平的、具有很少突起的对照细胞形成鲜明对比。它们的生长明显慢于对照细胞。他们还表现出明显较低的酪氨酸酶活性和黑色素生成潜力。我们认为，黑色素瘤相关的 O-乙酰基-GD3 神经节苷脂表达增强可能会刺激细胞生长并抑制某些分化表型，例如树突形成，但不会抑制黑色素生成。
The composition of the gangliosides of hamster melanoma cells is closely related to their cellular growth and degree of differentiation, with slow-growing, highly differentiated melanotic melanoma MI cells expressing GM3 and fast-growing, undifferentiated amelanotic Ab melanoma cells having a preponderance of GD3 and O-acetyl-GD3. To study the putative function of O-acetyl-GD3, we established stably transfected AbC-1 amelanotic hamster melanoma cells with O-acetylesterase gene from influenza C virus to hydrolyze the O-acetyl group from O-acetyl-GD3. The content of O-acetyl-GD3 in the transfected cells expressing O-acetylesterase gene was reduced by >90%. These O-acetyl-GD3-depleted cells differed from the parental ones in their cellular morphology, growth behavior, and melanogenesis activity. The absence of O-acetyl-GD3 in the transfected cells was accompanied by increased thick dendrite formation with an enlarged cell body, which is in striking contrast to the control cells, which were rounded and flattened, with few processes. Their growth was significantly slower than that of the control cells. They also demonstrated significantly lower tyrosinase activity and melanogenic potential. We suggest that the enhanced expression of melanoma-associated O-acetyl-GD3 ganglioside may stimulate cellular growth and suppress certain differentiated phenotypes such as dendrite formation but not melanogenesis.