Document Detail

Contrasting roles of p57(KIP2) and p21(WAF1/CIP1/SDI1) in transplanted human and bovine adrenocortical cells.
MedLine Citation:
PMID:  11339829     Owner:  NLM     Status:  MEDLINE    
Cell transplantation provides a way to compare the regulation of cell proliferation in the same cell type in cell culture and in a vascularized tissue structure in a host animal. The cyclin-dependent kinase inhibitors p57(KIP2), p21(WAF1/CIP1/SDI1) and p27(KIP1) have been extensively studied in cell culture but their role in growth control in tissues is less well understood. In the present experiments we compared the behavior of cell cycle inhibitors in human and bovine adrenocortical cells in culture and following cell transplantation in scid mice. p57 was expressed in the majority of cells in the intact human adrenal cortex. However, double immunofluorescence showed that cells that are in the cell cycle are p57(-) adrenocortical cells, p57 and p27 levels were not affected by inhibition of growth at high cell density, whereas p21 was higher in dividing than growth-inhibited cells. However, p21 was also high in senescent adrenocortical cells. After transplantation of human adrenocortical cells in scid mice, p57 and p27 were observed in most cells in the transplant tissue. Over time the number of p21(+) cells decreased greatly in human adrenocortical cells, but not in bovine adrenocortical cells. This difference correlated with lower levels of cell division (assessed by Ki-67 or incorporation of bromodeoxyuridine) in the human cells in transplant tissues in comparison to bovine cells. The differences between human and bovine cells were observed both when cells were transplanted beneath the kidney capsule and when cells were injected subcutaneously in collagen gel. We conclude that the behavior of p57, but not p21, is consistent with a role as a physiological mediator of proliferative quiescence in the adrenal cortex. The high level of p21 in dividing adrenocortical cells in culture, and in bovine adrenocortical cells in transplant tissues, may be a response to conflicting positive and negative growth influences. Cells may enter the cell cycle under the influence of a strong positive mitogenic signal, but coexisting negative growth stimuli trigger a p21-dependent block to further progression through the cell cycle. This model suggests that bovine adrenocortical cells respond to positive growth stimuli in transplant tissues but human cells lack this response.
M Thomas; N K Popnikolov; C Scott; J R Smith; P J Hornsby
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental cell research     Volume:  266     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-05-07     Completed Date:  2001-06-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  106-13     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Academic Press.
Huffington Center on Aging, Baylor College of Medicine, Houston, Texas 77030, USA.
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MeSH Terms
Adrenal Cortex / cytology,  metabolism*,  transplantation*
Bromodeoxyuridine / pharmacokinetics
Cell Culture Techniques / methods
Cell Cycle / physiology*
Cell Cycle Proteins*
Cells, Cultured / cytology,  metabolism*
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
Cyclin-Dependent Kinase Inhibitor p57
Cyclins / metabolism*
Graft Survival / physiology*
Microtubule-Associated Proteins / metabolism
Nuclear Proteins / metabolism*
Tissue Transplantation / methods
Tumor Suppressor Proteins*
Grant Support
Reg. No./Substance:
0/CDKN1A protein, human; 0/CDKN1C protein, human; 0/Cdkn1a protein, mouse; 0/Cdkn1b protein, mouse; 0/Cdkn1c protein, mouse; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclin-Dependent Kinase Inhibitor p57; 0/Cyclins; 0/Microtubule-Associated Proteins; 0/Nuclear Proteins; 0/Tumor Suppressor Proteins; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 59-14-3/Bromodeoxyuridine

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