Sundfeldt K, Ivarsson K, Carlsson M, Enerbäck S, Janson P O, Brännström M, Hedin L
Department of Physiology, Göteborg University, Sweden.
Br J Cancer. 1999 Mar;79(7-8):1240-8. doi: 10.1038/sj.bjc.6690199.
The CCAAT/enhancer binding protein (C/EBP) family of transcription factors is involved in metabolism and differentiation of cells, especially in rodent liver cells and adipocytes. Their roles in vivo and in particular during pathophysiological conditions in humans are largely unknown. We have investigated the presence of C/EBPalpha, -beta, -delta and -zeta in normal ovaries and in epithelial ovarian tumours of different stages. Immunohistochemical experiments demonstrated that C/EBPalpha and C/EBPbeta were preferentially expressed in epithelial/tumour cells irrespective of stage or grade of the tumour. C/EBPbeta was located in the nuclei of the cells, in contrast to C/EBPalpha, which was present only in the cytoplasm of these cells. The nuclear localization of C/EBPbeta indicates an active role of this transcription factor in tumour cells, whereas the cytoplasmic distribution suggests a more passive function of C/EBPalpha. C/EBPdelta and -zeta demonstrated a more diverse distribution with predominant localization to epithelial cells, but stromal distribution was also noted. The intracellular distribution was confined to both the nucleus and the cytoplasm for C/EBPdelta and -zeta. Western blotting demonstrated that C/EBPalpha, -beta, -delta and -zeta were present in a majority of the samples. The amount of C/EBPbeta increased markedly with malignancy, i.e. with degree of dedifferentiation, while the other members of the C/EBP family displayed a more constant expression level. These results demonstrate an association between the expression of members of the C/EBP family and the formation of epithelial ovarian tumours, with C/EBPbeta as a potential marker for these tumours. As C/EBPbeta is known to be expressed during proliferation of cells in vitro, it may participate in the proliferative process of ovarian epithelial tumour cells in vivo and play a central role in tumour progression.
CCAAT/增强子结合蛋白（C/EBP）转录因子家族参与细胞的代谢和分化，尤其是在啮齿动物肝细胞和脂肪细胞中。它们在体内的作用，特别是在人类病理生理条件下的作用，在很大程度上尚不清楚。我们研究了C/EBPα、-β、-δ和-ζ在正常卵巢以及不同阶段上皮性卵巢肿瘤中的存在情况。免疫组织化学实验表明，无论肿瘤的阶段或分级如何，C/EBPα和C/EBPβ均优先在上皮/肿瘤细胞中表达。与仅存在于这些细胞细胞质中的C/EBPα不同，C/EBPβ位于细胞核中。C/EBPβ的核定位表明该转录因子在肿瘤细胞中发挥积极作用，而C/EBPα的细胞质分布表明其功能较为被动。C/EBPδ和-ζ的分布更为多样，主要定位于上皮细胞，但也可见于基质。C/EBPδ和-ζ的细胞内分布局限于细胞核和细胞质。蛋白质印迹法表明，大多数样本中都存在C/EBPα、-β、-δ和-ζ。C/EBPβ的量随着恶性程度的增加，即去分化程度的增加而显著增加，而C/EBP家族的其他成员表达水平更为恒定。这些结果表明C/EBP家族成员的表达与上皮性卵巢肿瘤的形成之间存在关联，C/EBPβ是这些肿瘤的潜在标志物。由于已知C/EBPβ在体外细胞增殖过程中表达，它可能参与体内卵巢上皮肿瘤细胞的增殖过程，并在肿瘤进展中发挥核心作用。
