Niles R M, Combs R
Department of Biochemistry and Molecular Biology, Marshall University School of Medicine, Huntington, West Virginia 25755, USA.
Exp Cell Res. 1996 Feb 25;223(1):20-8. doi: 10.1006/excr.1996.0054.
Retinoic acid (RA)-induced differentiation of B16 mouse melanoma cells is accompanied by a large increase in the amount of PKCalpha protein. Overexpression of PKCalpha in these cells results in a more differentiated phenotype. To determine if these findings had general applicability to murine melanomas, we investigated the relationship between sensitivity to RA and induction of PKCalpha in three different murine melanoma cell lines. RA inhibited the anchorage-dependent growth of all three cell lines, with JB/MS being the most sensitive, S91 intermediate, and RPMI the least affected. RA also inhibited soft agar colony formation in JB/MS, but had little effect on RPMI. All cell lines expressed PKCalpha, but not beta or gamma. RA induced a large concentration-dependent increase in PKCalpha protein in JB/MS (6- to 10-fold), a smaller increase in S91 (2- to 3-fold), and very little induction of PKCalpha in RPMI. Previously we had observed that the amount of PKCalpha increased with the density of B16 cells in culture. We found that this density-dependent increase in PKCalpha occurred in three out of four melanoma cell lines examined. These results suggest that PKCalpha plays an important role in RA-induced murine melanoma cell differentiation.
维甲酸（RA）诱导的B16小鼠黑色素瘤细胞分化伴随着PKCα蛋白量的大幅增加。这些细胞中PKCα的过表达导致更分化的表型。为了确定这些发现是否普遍适用于鼠黑色素瘤，我们研究了三种不同鼠黑色素瘤细胞系中对RA的敏感性与PKCα诱导之间的关系。RA抑制了所有三种细胞系的贴壁依赖性生长，其中JB/MS最敏感，S91次之，RPMI受影响最小。RA还抑制了JB/MS在软琼脂中的集落形成，但对RPMI几乎没有影响。所有细胞系均表达PKCα，但不表达β或γ。RA在JB/MS中诱导PKCα蛋白大量浓度依赖性增加（6至10倍），在S91中增加较小（2至3倍），而在RPMI中对PKCα的诱导非常少。此前我们观察到PKCα的量随培养中B16细胞的密度增加而增加。我们发现，在所检测的四种黑色素瘤细胞系中，有三种出现了这种PKCα的密度依赖性增加。这些结果表明PKCα在RA诱导的鼠黑色素瘤细胞分化中起重要作用。
