Document Detail

Degrees and kinds of selection in spontaneous neoplastic transformation: an operational analysis.
MedLine Citation:
PMID:  15967983     Owner:  NLM     Status:  MEDLINE    
Spontaneous neoplastic transformation develops within days in the NIH 3T3 line of cells through differential inhibition of their proliferation under contact inhibition. A small fraction of the population continues to multiply after saturation density is reached and is selected to progressively increase saturation density in successive rounds of confluence. The degree of selection at confluence depends on the extent of proliferation of some cells in a heterogeneous population. The development of transformed foci is an extension of the same selective process that increases saturation density. The expression of the foci is enhanced with increases in the saturation density of the surrounding cells. Transformation is also induced by moderately reducing the concentration of calf serum in the medium during low-density passages, which allows selection of cells that require less growth factor. Further stepwise reductions in serum increase the degree of transformation. Contact inhibition and reduction in serum concentration select for the same phenotype of cell that increases saturation density and generates transformed foci. There is mounting evidence that selection is a major factor in the development of common epithelial tumors of humans, but it extends over decades rather than days, and the in vivo microenvironment selects from more stable populations of cells than those in culture. The many progressive levels of increased saturation density and transformed focus formation suggest that a very large number of genes participate in neoplastic development. The operational model of variation and selection presented here may aid in understanding chemical carcinogenesis and cancer recurrence after chemotherapy.
Harry Rubin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.     Date:  2005-06-20
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  102     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-06-29     Completed Date:  2005-08-11     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9276-81     Citation Subset:  IM    
Department of Molecular and Cell Biology, Life Sciences Addition, University of California, Berkeley, CA 94720-3200, USA.
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MeSH Terms
Cell Count
Cell Culture Techniques / methods*
Cell Line
Cell Line, Transformed*
Cell Lineage
Cell Proliferation
Cell Survival
Cell Transformation, Neoplastic*
Culture Media / pharmacology
Disease Progression
Genetic Predisposition to Disease*
NIH 3T3 Cells
Neoplasms / genetics*,  metabolism,  pathology
Time Factors
Grant Support
G13LM07483-03/LM/NLM NIH HHS
Reg. No./Substance:
0/Culture Media

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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