Expression of cyclins and cyclin dependent kinases in human benign and malignant melanocytic lesions^*

J Georgieva¹, P Sinha² and D Schadendorf¹

¹ Klinische Kooperationseinheit für Dermatoonkologie (DKFZ), Universitätsklinikum Mannheim, Universität Heidelberg, Theodor Kutzer Ufer 1, D-68135 Mannheim, Germany
² Institut für Laboratorium medizin und Pathobiochemie, Universtitätsklinikum Charité, Humboldt Universität zu Berlin, D–10117, Berlin, Germany

Correspondence to:
Dr Schadendorf d.schadendorf{at}dkfz-heidelberg.de

Aims—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.

Methods—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).

Results—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.

Conclusions—Taken together, this study demonstrated a significant increase of cyclin E and CDK2 expression during tumour progression in malignant melanomas.

Key Words: melanoma • immunohistology • naevus • cyclin E • cyclin dependent kinase 2 • cyclin B1

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Gollob, J. A., Sciambi, C. J., Huang, Z., Dressman, H. K. (2005). Gene Expression Changes and Signaling Events Associated with the Direct Antimelanoma Effect of IFN-{gamma}. Cancer Res. 65: 8869-8877 [Abstract] [Full Text]  
• Bales, E., Mills, L., Milam, N., McGahren-Murray, M., Bandyopadhyay, D., Chen, D., Reed, J. A., Timchenko, N., van den Oord, J. J., Bar-Eli, M., Keyomarsi, K., Medrano, E. E. (2005). The Low Molecular Weight Cyclin E Isoforms Augment Angiogenesis and Metastasis of Human Melanoma Cells In vivo. Cancer Res. 65: 692-697 [Abstract] [Full Text]  
• Bandyopadhyay, D., Okan, N. A., Bales, E., Nascimento, L., Cole, P. A., Medrano, E. E. (2002). Down-Regulation of p300/CBP Histone Acetyltransferase Activates a Senescence Checkpoint in Human Melanocytes. Cancer Res. 62: 6231-6239 [Abstract] [Full Text]