PMID- 7553653
OWN - NLM
STAT- MEDLINE
DCOM- 19951108
LR  - 20141120
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 55
IP  - 20
DP  - 1995 Oct 15
TI  - Differentiation of neuroblastoma enhances Bcl-2 expression and induces 
      alterations of apoptosis and drug resistance.
PG  - 4711-6
AB  - Recent evidence suggests that resistance to antineoplastic therapy may result 
      from mutations in genes mediating the apoptotic response to DNA damage. To 
      determine the effects of epigenetic changes on tumor responsiveness to cytotoxic 
      agents inducing DNA damage, we examined the chemosensitivity of neuroblastoma 
      (NB) after differentiation by retinoic acid (RA). Differentiation of the cell 
      lines SH-SY5Y and SMS-KCNR by RA abolished the cytotoxic effects of adriamycin 
      (Adr) and cisplatin. Chemoresistance was not the result of decreased 
      proliferation induced by RA because: (a) growth arrest by nutrient deprivation 
      did not affect sensitivity; (b) growth arrested NB cell lines, which did not 
      differentiate, remained chemosensitive; and (c) RA concentrations which promoted 
      differentiation without affecting growth, induced resistance. Apoptosis 
      characterized NB cells responding to Adr, although differentiated SH-SY5Y did not 
      apoptose and were resistant to Adr and cisplatin. Marked induction of bcl-2 in NB 
      cells followed RA-induced differentiation, whereas in cell lines failing to 
      differentiate, bcl-2 was not detected. Our data indicate that NB differentiation 
      induces drug resistance after a loss of the apoptotic response to antineoplastic 
      drugs and suggest that bcl-2 overexpression is an important mechanism of 
      resistance in differentiated tumor cells.
FAU - Lasorella, A
AU  - Lasorella A
AD  - Preuss Laboratory for Molecular Neuro-oncology, Department of Neurological 
      Surgery, University of California, San Francisco 94143-0520, USA.
FAU - Iavarone, A
AU  - Iavarone A
FAU - Israel, M A
AU  - Israel MA
LA  - eng
GR  - 5P20 NS31076/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 5688UTC01R (Tretinoin)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Apoptosis/drug effects
MH  - *Cell Differentiation/drug effects
MH  - Doxorubicin/toxicity
MH  - Drug Resistance, Neoplasm
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Genes, myc
MH  - Humans
MH  - In Vitro Techniques
MH  - Neuroblastoma/*pathology
MH  - Neurons/cytology
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-bcl-2
MH  - RNA, Messenger/genetics
MH  - Tretinoin/pharmacology
MH  - Tumor Cells, Cultured
EDAT- 1995/10/15 00:00
MHDA- 1995/10/15 00:01
CRDT- 1995/10/15 00:00
PHST- 1995/10/15 00:00 [pubmed]
PHST- 1995/10/15 00:01 [medline]
PHST- 1995/10/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1995 Oct 15;55(20):4711-6.