Manzow S, Brancolini C, Marks F, Richter K H
Biochemistry of Tissue Specific Regulation, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Exp Cell Res. 1996 Apr 10;224(1):200-3. doi: 10.1006/excr.1996.0128.
In order to elucidate a possible role of growth arrest-specific (gas) genes in the regulation of tissue proliferation, we analyzed their expression in keratinocytes isolated from murine back skin. On the mRNA level gas1, gas5, and gas6 were found to be significantly expressed whereas there was a relatively low expression of gas2, gas3, and gas4. Using keratinocytes fractionated according to their density resulted in subpopulations of cells: differentiating suprabasal cells in fractions I and II; proliferative basal cells in fractions IIIa, III and IV. We found gas2 protein to be expressed more strongly in the proliferative cells than in the differentiating cells. Stimulation of hyperproliferation by 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a transient increase of gas2 protein content concomitantly with the time of maximal cell renewal. In this respect the murine keratinocyte cell line MSCP5 resembled freshly isolated keratinocytes. There was a higher expression of gas2 protein during exponential growth than during growth arrest, induced either by serum starvation or by TGFbeta treatment. Since, in contrast to the results reported for 3T3 cells, growth arrest within these cells was not accompanied by an elevation of gas2 protein, we suggest a cell-specific regulation of its expression.
为了阐明生长停滞特异性(gas)基因在组织增殖调节中的可能作用,我们分析了从鼠背部皮肤分离的角质形成细胞中这些基因的表达。在mRNA水平上,发现gas1、gas5和gas6有显著表达,而gas2、gas3和gas4的表达相对较低。根据密度对角质形成细胞进行分级分离,得到了不同的细胞亚群:I和II级分中的分化上层基底细胞;IIIa、III和IV级分中的增殖基底细胞。我们发现gas2蛋白在增殖细胞中的表达比在分化细胞中更强。12-O-十四烷酰佛波醇-13-乙酸酯(TPA)刺激过度增殖导致gas2蛋白含量短暂增加,同时伴随着最大细胞更新时间。在这方面,鼠角质形成细胞系MSCP5类似于新鲜分离的角质形成细胞。指数生长期的gas2蛋白表达高于血清饥饿或TGFβ处理诱导的生长停滞期。由于与3T3细胞报道的结果相反,这些细胞中的生长停滞并未伴随着gas2蛋白的升高,我们认为其表达存在细胞特异性调节。