Expression of cell cycle regulators in human cutaneous malignant melanoma.
We postulate that genes involved in the control of cell proliferation are important determinants of melanoma growth and/or transformation. Using Western blot analysis, we compared the expression of nine key cell cycle regulators in metastatic melanomas with that in benign acquired naevi. Among the cyclin-dependent kinases (CDKs) examined, CDK2 was consistently and significantly overexpressed (three- to eight-fold) in metastatic melanomas compared with naevi. CDK1 and CDK4 exhibited no significant difference in expression between benign naevi and metastatic melanomas. CDK6 expression was variable, with four out of 10 metastatic melanomas showing higher expression than naevi. All the cyclins examined, especially cyclins A and D, were expressed more in metastatic melanomas than in naevi. Cyclin E was not detected in benign naevi, but was easily detectable in most of the metastatic melanomas. In addition, there was significantly greater expression of CDC25A, a tyrosine phosphatase that activates CDK kinases, in the metastatic melanomas. Over-expression of CDK2, CDK6, CDC25A and cyclin A was confirmed in melanoma cell lines. These cell cycle regulators may play an important role in melanoma growth and/or transformation.
Tang
L
L
Department of Medicine, Vancouver Hospital and Health Sciences Center, BC, Canada.
Li
G
G
Tron
V A
VA
Trotter
M J
MJ
Ho
V C
VC
D015153:Blotting, Western; D042846:CDC2-CDC28 Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D019925:Cyclin A / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D020687:cdc25 Phosphatases
D018797:Cell Cycle Proteins; D019925:Cyclin A; D019927:Cyclin E; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; C517004:CDC25A protein, human; D017027:Protein Tyrosine Phosphatases; D020687:cdc25 Phosphatases