PMID- 11181703
OWN - NLM
STAT- MEDLINE
DCOM- 20010517
LR  - 20240213
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 193
IP  - 4
DP  - 2001 Feb 19
TI  - Role of promyelocytic leukemia (PML) protein in tumor suppression.
PG  - 521-29
AB  - The promyelocytic leukemia (PML) gene encodes a putative tumor suppressor gene 
      involved in the control of apoptosis, which is fused to the retinoic acid 
      receptor alpha (RARalpha) gene in the vast majority of acute promyelocytic 
      leukemia (APL) patients as a consequence of chromosomal translocations. The 
      PMLRARalpha oncoprotein is thought to antagonize the function of PML through its 
      ability to heterodimerize with and delocalize PML from the nuclear body. In APL, 
      this may be facilitated by the reduction to heterozygosity of the normal PML 
      allele. To determine whether PML acts as a tumor suppressor in vivo and what the 
      consequences of deregulated programmed cell death in leukemia and epithelial 
      cancer pathogenesis are, we crossed PML(-/-) mice with human cathepsin G 
      (hCG)-PMLRARalpha or mammary tumor virus (MMTV)/neu transgenic mice (TM), models 
      of leukemia and breast cancer, respectively. The progressive reduction of the 
      dose of PML resulted in a dramatic increase in the incidence of leukemia, and in 
      an acceleration of leukemia onset in PMLRARalpha TM. By contrast, PML 
      inactivation did not affect neu-induced tumorigenesis. In hemopoietic cells from 
      PMLRARalpha TM, PML inactivation resulted in impaired response to differentiating 
      agents such as RA and vitamin D3 as well as in a marked survival advantage upon 
      proapoptotic stimuli. These results demonstrate that: (a) PML acts in vivo as a 
      tumor suppressor by rendering the cells resistant to proapoptotic and 
      differentiating stimuli; (b) PML haploinsufficiency and the functional impairment 
      of PML by PMLRARalpha are critical events in APL pathogenesis; and (c) aberrant 
      control of programmed cell death plays a differential role in solid tumor and 
      leukemia pathogenesis.
FAU - Rego, E M
AU  - Rego EM
AD  - Department of Human Genetics and Molecular Biology Program, Memorial 
      Sloan-Kettering Cancer Center, New York, New York 10021, USA.
FAU - Wang, Z G
AU  - Wang ZG
FAU - Peruzzi, D
AU  - Peruzzi D
FAU - He, L Z
AU  - He LZ
FAU - Cordon-Cardo, C
AU  - Cordon-Cardo C
FAU - Pandolfi, P P
AU  - Pandolfi PP
LA  - eng
GR  - CA74031/CA/NCI NIH HHS/United States
GR  - R01 CA071692/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R01 CA074031/CA/NCI NIH HHS/United States
GR  - CA71692/CA/NCI NIH HHS/United States
GR  - R37 CA071692/CA/NCI NIH HHS/United States
GR  - CA08748/CA/NCI 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  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Pml protein, mouse)
RN  - 0 (Promyelocytic Leukemia Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (fas Receptor)
RN  - 0 (promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein)
RN  - 1C6V77QF41 (Cholecalciferol)
SB  - IM
CIN - J Exp Med. 2001 Feb 19;193(4):F15-8. PMID: 11181707
MH  - Animals
MH  - Apoptosis/genetics
MH  - Cholecalciferol/pharmacology
MH  - Disease-Free Survival
MH  - Female
MH  - *Genes, Tumor Suppressor
MH  - Leukemia, Promyelocytic, Acute/etiology/*genetics/mortality
MH  - Mammary Neoplasms, Experimental/etiology/genetics/mortality
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mice, Transgenic
MH  - Neoplasm Proteins/*genetics
MH  - *Nuclear Proteins
MH  - Oncogene Proteins, Fusion/genetics
MH  - Promyelocytic Leukemia Protein
MH  - Transcription Factors/*genetics
MH  - Tumor Suppressor Proteins
MH  - fas Receptor/metabolism
PMC - PMC2195907
EDAT- 2001/02/22 11:00
MHDA- 2001/05/18 10:01
PMCR- 2001/08/19
CRDT- 2001/02/22 11:00
PHST- 2001/02/22 11:00 [pubmed]
PHST- 2001/05/18 10:01 [medline]
PHST- 2001/02/22 11:00 [entrez]
PHST- 2001/08/19 00:00 [pmc-release]
AID - 001443 [pii]
AID - 10.1084/jem.193.4.521 [doi]
PST - ppublish
SO  - J Exp Med. 2001 Feb 19;193(4):521-29. doi: 10.1084/jem.193.4.521.