P21 and Bax expression in cutaneous malignant melanomas: correlation with histologic prognostic parameters.
In response to DNA damage, p53 accumulates and regulates expression of several genes, including cyclin-dependent kinase inhibitor p21. Cells then undergo p21 dependent cell cycle arrest, which allows DNA damage repair and apoptosis. Bax is a death promoter member of the bcl-2 family which plays a central role in the regulation and commitment to programmed cell death. Breslow thickness is the most important factor in predicting prognosis for cutaneous malignant melanoma. In order to define the role of cyclin dependent kinase inhibitors and apoptosis regulators in invasion of malignant melanoma we investigated the expression of p21 and bax proteins. We observed that significant high p21 expression was associated with increasing Breslow thickness (Spearman correlation analysis, p=0.01). Additionally, Clark level I and II tumours expressed significantly lower p21 positivity than Clark level III, IV and V (p=0.006). Similarly, thick tumors showed a higher bax expression (p=0.012). Our results suggested that the role of p21 expression is more complicated in melanocytic skin cancers and abnormal regulation or abnormal function of cell cycle regulators occurred in the development and progression of malignant melanoma. In order to understand the role of bax expression in thick malignant melanomas and invasion biology, comparative analytic studies with other apoptosis regulators are needed.
Poyraz
A
A
Dept. of Pathology, Gazi University Medical School, Ankara, Turkey. aylarpoyraz@yahoo.com
Akyürek
N
N
Gönül
I I
II
Erdem
O
O
D000328:Adult; D000368:Aged; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D003593:Cytoplasm / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein