Expressions of cyclin E, A, and B1 in Hodgkin and Reed-Sternberg cells: not suppressed by cyclin-dependent kinase inhibitor p21 expression.
p21 Is involved in the control of the mammalian cell cycle through the binding and inhibition of cyclin-dependent kinases. The cyclins are dependent on the phases of the cell cycle, and divided into two classes: mitotic cyclins (A, B1, B2) and G1 cyclins (C, D1, D2, D3, E). The product of the p21 gene is a potent downstream effector of the p53 tumor-suppressor gene function. The Hodgkin and Reed- Sternberg (H & RS) cells in Hodgkin's disease are reported to frequently express p53, p21, and nuclear proliferative activity (Ki-67). To clarify the relationship of p21, p53 and cyclins, we performed the immunohistochemistry of p53, p21, Ki-67, cyclin D1, cyclin E, cyclin A and cyclin B1, using 11 cases with Hodgkin's disease. In addition, we performed p53 gene sequencing of exon 5-8, and in situ hybridization of Epstein-Barr virus (EBV) EBER-1 region, whose products have reported to induce the expression of cyclin D. In this study, in all cases, Ki-67 was expressed in almost all H & RS cells, and p53 and p21 were expressed in H & RS cells. No p53 gene mutations were detected in any case, and p53 protein overexpression did not correlate with p53 gene mutations. The number of p21-positive H & RS cells was significantly related with that of the p53-positive cells. The cyclins E, A, B1 and D1 were also expressed in H & RS cells. Unexpectedly, the expression of the cyclins was not suppressed by p21 and p53 expression. In addition, the existence of EBV was not related to the expression of cyclins. It is considered that H & RS cells are, indeed, in cell cycle and commonly express the cell cyclins, and that the cell cycle of H & RS cells may not be specifically fixed in the G1, S, G2 or M phases.
Ohshima
K
K
Department of Pathology, School of Medicine, Fukuoka University, Nanakuma, Japan.
Haraoka
S
S
Fujiki
T
T
Yoshioka
S
S
Suzumiya
J
J
Kanda
M
M
Kikuchi
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D002648:Child; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000378:metabolism; D005260:Female; D015967:Gene Expression Regulation, Viral; D006689:Hodgkin Disease / Q000378:metabolism* / Q000821:virology; D006801:Humans; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D016539:Reed-Sternberg Cells / Q000378:metabolism* / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D004791:Enzyme Inhibitors; C099537:Epstein-Barr virus encoded RNA 1; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53