胶质瘤细胞c-fos和c-myc基因表达与血小板源生长因子B链的纯合二聚体自分泌环活性的观察

Observations on expression of cfos and cmyc genes and activity of PDGFBB autocrine loop in 67 human gliomas

目的探讨胶质瘤细胞ｃｆｏｓ和ｃｍｙｃ基因表达和血小板源生长因子（ＰＤＧＦ）Ｂ链的纯合二聚体（ＢＢ）自分泌环活性的改变及其相互关系。方法用原位杂交和免疫组化方法观察了６７例人胶质瘤组织。结果６７例中，ｃｆｏｓｍＲＮＡ、ｃｆｏｓ蛋白、ｃｍｙｃｍＲＮＡ及ｃｍｙｃ蛋白阳性率分别为：１００％、１００％、８５１％、８３６％。ｃｆｏｓｍＲＮＡ（９２４９±３３８７）与ｃｆｏｓ蛋白（９１６４±３８１１）及ｃｍｙｃｍＲＮＡ（７２７０±４０５６）与ｃｍｙｃ蛋白（７１４９±４１１１）阳性肿瘤细胞密度（ｘ±ｓ，个／００５ｍｍ２）间均呈正相关（ｒ＝０．９１７～０．９８８，Ｐ＜０．００１），并均随肿瘤恶性程度及肿瘤细胞ＰＤＧＦＢｍＲＮＡ表达水平升高而相应增加（Ｐ＜０．０５～０．０１）。ＰＤＧＦα受体（５８４６±２８７７）、β受体（６３０３±３１６３）及酪氨酸磷酸化蛋白（６８２５±２９３０）阳性肿瘤细胞密度（ｘ±ｓ，个／００５ｍｍ２）间均呈正相关（ｒ＝０．８２７～０．８９６，Ｐ＜０．００１），并均分别与ＰＤＧＦＢｍＲＮＡ（７１７３±４３４２）、ｃｆｏｓｍＲＮＡ、ｃｆｏｓ蛋白、?

Objective To investigate the variance of expression of cfos and cmyc genes and the activity of plateletderived growth factor (PDGF) BB autocrine loop in human gliomas as well as their relationship. Methods In situ hybridization and immunohistochemistry were used to study 67 human glioma specimens of different grades. Results The incidences, of positive expression for cfos mRNA, cfos protein, cmyc mRNA and cmyc protein were 100% (67/67), 100% (67/67), 851% (57/67) and 836% (56/67) respectively. There was significant positive correlation between the positive cell densities of cfos mRNA (92493387) and cfos protein(91643811), and of cmyc mRNA (72704056) and cmyc protein (71494111,r=09170988, P<0001). All of them also increased correspondingly with the malignant degree of the tumors and level of PDGFB mRNA expression in the tumor cells (P<005001). Not only were the positive cell densities of PDGF receptor (58462877), PDGF receptor (63033163) and phosphotyrosine protein (68252930) correlated positively with one another (r=08270896, P<0001), but they also all correlated positively with the positive cell densities of PDGFB mRNA, cfos mRNA, cfos protein, cmyc mRNA and cmyc protein respectively (r=06150888, P<0001). Conclusions The abnormally increased activity of the PDGFBB autocrine loop possibly upregulated the overexpression of cfos and cmyc genes in glioma cells and suggested that cfos and cmyc proteins probably played an important role as downstream response factors in the signaling pathway in which PDGFBB could induce gliocyte transformation and glioma development.