Georgieva J, Sinha P, Schadendorf D
Klinische Kooperationseinheit für Dermatoonkologie (DKFZ), Universitätsklinikum Mannheim, Universität Heidelberg, Germany.
J Clin Pathol. 2001 Mar;54(3):229-35. doi: 10.1136/jcp.54.3.229.
The regulation of cell proliferation is a key event in normal development, pathophysiological responses to injury, and tumorigenesis. The orderly progression of cells through the cell cycle depends on a finely tuned balance between the concentrations of activated cyclins and cyclin dependent kinases. This study was undertaken to compare the expression of cell cycle regulators in benign and malignant melanocytic lesions during tumour progression.
Immunohistochemistry was used to analyse 49 primary cutaneous malignant melanomas, 18 metastatic melanomas, and 12 histologically confirmed naevus cell naevi for their expression of cyclins (A, B1, D1, D2, D3, and E) and cyclin dependent kinases (CDK1, CDK2, and CDK4).
Cyclin E and CDK2 had the highest expression patterns in human cutaneous melanomas and metastases and correlated positively with histological type and tumour stage. Cyclins B1, D2, and D3 had significantly increased expression in metastases, but normal or even decreased expression in primary melanomas. However, cyclins A and D1, and CDK1 and CDK4 were expressed very weakly in situ with no significant differences between naevi, melanomas, or metastases, and there was no correlation with histopathological staging. The specificity of recognition by the antibodies used was confirmed by western blotting on a panel of seven human melanoma cell lines. Cyclins A, B, and E were expressed by all seven, whereas cyclin D1 was detectable in six of seven and CDK2 and cdc2 were present in five of seven lines analysed.
Taken together, this study demonstrated a significant increase of cyclin E and CDK2 expression during tumour progression in malignant melanomas.
细胞增殖的调控是正常发育、损伤的病理生理反应以及肿瘤发生过程中的关键事件。细胞通过细胞周期的有序进展取决于活化细胞周期蛋白和细胞周期蛋白依赖性激酶浓度之间的精确平衡。本研究旨在比较肿瘤进展过程中良性和恶性黑素细胞性病变中细胞周期调节因子的表达情况。
采用免疫组织化学方法分析49例原发性皮肤恶性黑色素瘤、18例转移性黑色素瘤和12例经组织学证实的痣细胞痣中细胞周期蛋白（A、B1、D1、D2、D3和E）和细胞周期蛋白依赖性激酶（CDK1、CDK2和CDK4）的表达情况。
细胞周期蛋白E和CDK2在人类皮肤黑色素瘤和转移灶中的表达模式最高，且与组织学类型和肿瘤分期呈正相关。细胞周期蛋白B1、D2和D3在转移灶中的表达显著增加，但在原发性黑色素瘤中表达正常甚至降低。然而，细胞周期蛋白A和D1以及CDK1和CDK4在原位表达非常微弱，痣、黑色素瘤或转移灶之间无显著差异，且与组织病理学分期无关。通过对一组七种人类黑色素瘤细胞系进行蛋白质印迹分析，证实了所用抗体识别的特异性。七种细胞系均表达细胞周期蛋白A、B和E，而七种中有六种可检测到细胞周期蛋白D1，在分析的七种细胞系中有五种存在CDK2和cdc2。
综上所述，本研究表明在恶性黑色素瘤的肿瘤进展过程中，细胞周期蛋白E和CDK2的表达显著增加。
