PMID- 20442289
OWN - NLM
STAT- MEDLINE
DCOM- 20100621
LR  - 20181201
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 70
IP  - 10
DP  - 2010 May 15
TI  - Deficiency in p53 but not retinoblastoma induces the transformation of 
      mesenchymal stem cells in vitro and initiates leiomyosarcoma in vivo.
PG  - 4185-94
LID - 10.1158/0008-5472.CAN-09-4640 [doi]
AB  - Sarcomas have been modeled in mice by the expression of specific fusion genes in 
      mesenchymal stem cells (MSC), supporting the concept that MSCs might be the 
      target initiating cell in sarcoma. In this study, we evaluated the potential 
      oncogenic effects of p53 and/or retinoblastoma (Rb) deficiency in MSC 
      transformation and sarcomagenesis. We derived wild-type, p53(-/-), Rb(-/-), and 
      p53(-/-)Rb(-/-) MSC cultures and fully characterized their in vitro growth 
      properties and in vivo tumorigenesis capabilities. In contrast with wild-type 
      MSCs, Rb(-/-), p53(-/-), and p53(-/-)Rb(-/-) MSCs underwent in vitro 
      transformation and showed severe alterations in culture homeostasis. More 
      importantly, p53(-/-) and p53(-/-)Rb(-/-) MSCs, but not Rb(-/-) MSCs, were 
      capable of tumor development in vivo after injection into immunodeficient mice. 
      p53(-/-) or p53(-/-)Rb(-/-) MSCs originated leiomyosarcoma-like tumors, linking 
      this type of smooth muscle sarcoma to p53 deficiency in fat tissue-derived MSCs. 
      Sca1+ and Sca1 low/- cell populations isolated from ex vivo-established, 
      transformed MSC lines from p53(-/-)Rb(-/-) tumors showed identical sarcomagenesis 
      potential, with 100% tumor penetrance and identical latency, tumor weight, and 
      histologic profile. Our findings define the differential roles of p53 and Rb in 
      MSC transformation and offer proof-of-principle that MSCs could provide useful 
      tools to dissect the sarcoma pathogenesis.
CI  - (c)2010 AACR.
FAU - Rubio, Ruth
AU  - Rubio R
AD  - Andalusian Stem Cell Bank, Centro de Investigacion Biomedica, Consejeria de 
      Salud-Universidad de Granada, Granada, Spain.
FAU - Garcia-Castro, Javier
AU  - Garcia-Castro J
FAU - Gutierrez-Aranda, Ivan
AU  - Gutierrez-Aranda I
FAU - Paramio, Jesus
AU  - Paramio J
FAU - Santos, Mirentxu
AU  - Santos M
FAU - Catalina, Purificacion
AU  - Catalina P
FAU - Leone, Paola E
AU  - Leone PE
FAU - Menendez, Pablo
AU  - Menendez P
FAU - Rodriguez, Rene
AU  - Rodriguez R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100504
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (RNA, Messenger)
RN  - 0 (Retinoblastoma Protein)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.7.- (Cre recombinase)
RN  - EC 2.7.7.- (Integrases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Adhesion
MH  - Cell Differentiation
MH  - Cell Movement
MH  - Cell Proliferation
MH  - *Cell Transformation, Neoplastic
MH  - Fluorescent Antibody Technique
MH  - In Vitro Techniques
MH  - Integrases/metabolism
MH  - Leiomyosarcoma/metabolism/*pathology
MH  - Mesenchymal Stem Cells/*pathology
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, Knockout
MH  - Mice, SCID
MH  - RNA, Messenger/genetics/metabolism
MH  - Retinoblastoma Protein/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sarcoma, Experimental/metabolism/*pathology
MH  - Tumor Suppressor Protein p53/*physiology
EDAT- 2010/05/06 06:00
MHDA- 2010/06/22 06:00
CRDT- 2010/05/06 06:00
PHST- 2010/05/06 06:00 [entrez]
PHST- 2010/05/06 06:00 [pubmed]
PHST- 2010/06/22 06:00 [medline]
AID - 0008-5472.CAN-09-4640 [pii]
AID - 10.1158/0008-5472.CAN-09-4640 [doi]
PST - ppublish
SO  - Cancer Res. 2010 May 15;70(10):4185-94. doi: 10.1158/0008-5472.CAN-09-4640. Epub 
      2010 May 4.