Document Detail

Differential apoptotic behaviors of c-myc, N-myc, and L-myc oncoproteins.
MedLine Citation:
PMID:  9751117     Owner:  NLM     Status:  MEDLINE    
c-, N-, and L-myc are related nuclear oncoproteins that bind similar DNA sites and cooperate with activated ras oncogenes to transform primary fibroblasts. Although c-myc can also promote apoptosis in some cells after growth factor withdrawal or exposure to cytotoxic agents, roles for N- and L-myc in apoptosis remain undetermined. To address this, c-, N-, or L-myc were stably expressed in the interleukin 3 (IL-3)-dependent 32D hematopoietic cell line. The apoptotic response of each cell line was assessed after IL-3 withdrawal or treatment with four structurally unrelated cytotoxic agents. All three oncoproteins accelerated apoptosis after IL-3 withdrawal. In contrast, whereas c-myc overexpression generally sensitized cells to cytotoxic drugs, N-myc and L-myc overexpression produced resistance. myc expression tended to be associated with a more robust G2-M arrest after drug exposure, but this did not correlate with drug sensitivity or resistance. Bcl-2 and Bcl-X(L) protected control cells against apoptosis after either IL-3 withdrawal or drug exposure, although in some cases this effect could be overridden by myc oncoproteins, particularly N-myc and L-myc. Our results suggest that the apoptotic pathways activated upon IL-3 withdrawal and cytotoxic drug treatment are distinct and differentially affected by members of the myc and Bcl-2 families.
C E Nesbit; L E Grove; X Yin; E V Prochownik
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research     Volume:  9     ISSN:  1044-9523     ISO Abbreviation:  Cell Growth Differ.     Publication Date:  1998 Sep 
Date Detail:
Created Date:  1998-12-11     Completed Date:  1998-12-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9100024     Medline TA:  Cell Growth Differ     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  731-41     Citation Subset:  IM    
Department of Pediatrics, Children's Hospital of Pittsburgh, Pennsylvania 15213, USA.
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MeSH Terms
Antineoplastic Agents / pharmacology
Apoptosis / drug effects,  genetics,  physiology*
Cell Line
Culture Media / chemistry,  metabolism,  pharmacology
Interleukin-3 / deficiency
Proto-Oncogene Proteins c-bcl-2 / genetics,  physiology
Proto-Oncogene Proteins c-myc / genetics,  physiology*
bcl-X Protein
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents; 0/Culture Media; 0/Interleukin-3; 0/Proto-Oncogene Proteins c-bcl-2; 0/Proto-Oncogene Proteins c-myc; 0/bcl-X Protein

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