Negative regulation of mitogen-stimulated, anchorage-independent cell growth by a tumor-suppressor gene function

1993 ◽  
Vol 7 (4) ◽  
pp. 249-256 ◽  
Author(s):  
Cynthia A. Afshari ◽  
J. Carl Barrett
Keyword(s):  
Cell Growth ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Gene Function ◽  
Suppressor Gene ◽  
Negative Regulation ◽  
Tumor Suppressor Gene Function

scholarly journals p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: a potential marker of p53 tumor-suppressor gene function

Blood ◽  
1996 ◽  
Vol 88 (10) ◽  
pp. 4012-4020 ◽  
Author(s):  
M Chilosi ◽  
C Doglioni ◽  
A Magalini ◽  
G Inghirami ◽  
M Krampera ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Gene Function ◽  
Gene Mutations ◽  
P53 Gene ◽  
Suppressor Gene ◽  
P53 Tumor Suppressor ◽  
P53 Tumor Suppressor Gene ◽  
Hodgkin's Lymphomas ◽  
Tumor Suppressor Gene Function

p21WAF1 (wild-type p53-activated fragment 1) is involved in the control of mammalian cell cycle through the binding and inhibition of cyclin-dependent kinases (Cdk). Because the product of WAF1 gene is a potent downstream effector of the p53 tumor-suppressor gene function, its pattern of cellular expression might correlate with nuclear accumulation of p53-encoded protein and/or p53 gene mutations occurring in malignant lymphomas. To investigate this issue, we analyzed immunohistochemically the expression of p53 and p21WAF1 proteins in tissue involved by non-Hodgkin's lymphomas (NHLs;253 cases) of various histologic types. In a proportion of them (80 cases), we also investigated the possible presence of p53 gene mutations using single- strand conformation polymorphism analysis and direct DNA sequencing. The absence of both p21WAF1 and p53 proteins was observed in 147 of 217 cases (67.7%) among CD30-NHL and in only 8 of 36 (22.2%) CD30+cases, which were mostly anaplastic large-cell lymphomas. A consistent number (> 10%) of p21WAF1-expressing cells was shown in 48 of 253 (18.9%) NHL cases, with a higher incidence in CD30+cases (25/36 [69.4%]), which mostly (21/36) coexpressed p53. These latter cases were characterized by a germline configuration of the p53 gene. In 50 of 253 NHL samples (19.7%), 47 of which (21.6%) belong to the CD30-group, neoplastic cells were p53+/p21-. In all of these cases, the p53+cells accounted for more than 50% of neoplastic cells, up to 100%. Point mutations of p53 gene were solely observed in all investigated cases with this latter phenotype. Our findings strongly suggest that the combined immunohistochemical evaluation of p53 and p21WAF1 is a valuable means of assessing the functional status of the p53 tumor-suppressor gene product in NHL with potential application in the monitorage and prognostication of individual cases.

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