Document Detail

Epidermal cell-shape regulation and subpopulation kinetics during butyrate-induced terminal maturation of normal and SV40-transformed human keratinocytes: epithelial models of differentiation therapy.
MedLine Citation:
PMID:  2210888     Owner:  NLM     Status:  MEDLINE    
Recent data indicate that malignant human epidermal cells may be appropriate targets for sodium butyrate (NaB)-mediated differentiation therapy. The response of pre- and post-crisis populations of SV40-transformed human keratinocytes (SVKs) to this differentiation-inducing agent was assessed, therefore, within the framework of NaB-directed normal human keratinocyte (NHK) maturation. NaB augmented cornified envelope (CE) production in NHK and pre-crisis SVK cultures; the time-course and efficiency of induced maturation were similar in the 2 cell systems. In NHKs, the percentage of amplifying ("B" substate) cells decreased with time in NaB correlating with increases in both "C" stage keratinocytes and CEs. The latter formed over one or 2 layers of nucleated basal-like cells. Inductions were accompanied by immediate cell cycle blocks (in both the G1 and G2/M phases), reorganization within the actin cytoskeleton, and transient early increases in cellular actin content. Increased NHK and pre-crisis SVK cytoskeletal-associated actin reached a maximum approximately 48 hr after NaB addition and preceded development of CEs. The CE precursors, thus, probably reside in the "B" substate. Post-crisis SVKs, in contrast, were refractive to NaB-induced terminal maturation or cell-cycle perturbation, failed to initiate actin filament rearrangements, and retained a basal cell-like phenotype. Stable transformation of human SVKs in post-crisis phase, therefore, appears to be associated with loss of maturation "competence" within the "B" keratinocyte subpopulation.
L Staiano-Coico; M Steinberg; P J Higgins
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  46     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  1990 Oct 
Date Detail:
Created Date:  1990-11-20     Completed Date:  1990-11-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  733-8     Citation Subset:  IM    
Department of Surgery, Cornell University Medical Center, New York, NY 10021.
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MeSH Terms
Actins / biosynthesis
Blotting, Western
Butyric Acid
Butyric Acids / pharmacology*
Cell Cycle / drug effects
Cell Transformation, Viral / drug effects*
Intermediate Filaments / metabolism
Keratinocytes / drug effects*,  pathology
Microfilaments / metabolism,  ultrastructure
Grant Support
Reg. No./Substance:
0/Actins; 0/Butyric Acids; 107-92-6/Butyric Acid

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