PMID- 19092805
OWN - NLM
STAT- MEDLINE
DCOM- 20090311
LR  - 20250214
IS  - 1476-4687 (Electronic)
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 457
IP  - 7229
DP  - 2009 Jan 29
TI  - Prominin 1 marks intestinal stem cells that are susceptible to neoplastic 
      transformation.
PG  - 603-7
LID - 10.1038/nature07589 [doi]
AB  - Cancer stem cells are remarkably similar to normal stem cells: both self-renew, 
      are multipotent and express common surface markers, for example, prominin 1 
      (PROM1, also called CD133). What remains unclear is whether cancer stem cells are 
      the direct progeny of mutated stem cells or more mature cells that reacquire stem 
      cell properties during tumour formation. Answering this question will require 
      knowledge of whether normal stem cells are susceptible to cancer-causing 
      mutations; however, this has proved difficult to test because the identity of 
      most adult tissue stem cells is not known. Here, using an inducible Cre, nuclear 
      LacZ reporter allele knocked into the Prom1 locus (Prom1(C-L)), we show that 
      Prom1 is expressed in a variety of developing and adult tissues. Lineage-tracing 
      studies of adult Prom1(+/C-L) mice containing the Rosa26-YFP reporter allele 
      showed that Prom1(+) cells are located at the base of crypts in the small 
      intestine, co-express Lgr5 (ref. 2), generate the entire intestinal epithelium, 
      and are therefore the small intestinal stem cell. Prom1 was reported recently to 
      mark cancer stem cells of human intestinal tumours that arise frequently as a 
      consequence of aberrant wingless (Wnt) signalling. Activation of endogenous Wnt 
      signalling in Prom1(+/C-L) mice containing a Cre-dependent mutant allele of 
      beta-catenin (Ctnnb1(lox(ex3))) resulted in a gross disruption of crypt 
      architecture and a disproportionate expansion of Prom1(+) cells at the crypt 
      base. Lineage tracing demonstrated that the progeny of these cells replaced the 
      mucosa of the entire small intestine with neoplastic tissue that was 
      characterized by focal high-grade intraepithelial neoplasia and crypt adenoma 
      formation. Although all neoplastic cells arose from Prom1(+) cells in these mice, 
      only 7% of tumour cells retained Prom1 expression. Our data indicate that Prom1 
      marks stem cells in the adult small intestine that are susceptible to 
      transformation into tumours retaining a fraction of mutant Prom1(+) tumour cells.
FAU - Zhu, Liqin
AU  - Zhu L
AD  - Department of Developmental Neurobiology, St Jude Children's Research Hospital, 
      262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
FAU - Gibson, Paul
AU  - Gibson P
FAU - Currle, D Spencer
AU  - Currle DS
FAU - Tong, Yiai
AU  - Tong Y
FAU - Richardson, Robert J
AU  - Richardson RJ
FAU - Bayazitov, Ildar T
AU  - Bayazitov IT
FAU - Poppleton, Helen
AU  - Poppleton H
FAU - Zakharenko, Stanislav
AU  - Zakharenko S
FAU - Ellison, David W
AU  - Ellison DW
FAU - Gilbertson, Richard J
AU  - Gilbertson RJ
LA  - eng
GR  - R01 CA129541/CA/NCI NIH HHS/United States
GR  - P01CA96832/CA/NCI NIH HHS/United States
GR  - R01 CA129541-02/CA/NCI NIH HHS/United States
GR  - P30CA021765/CA/NCI NIH HHS/United States
GR  - R01 CA129541-01/CA/NCI NIH HHS/United States
GR  - P30 CA021765/CA/NCI NIH HHS/United States
GR  - R01 MH079079/MH/NIMH NIH HHS/United States
GR  - R01 MH079079-02/MH/NIMH NIH HHS/United States
GR  - R01 MH079079-04/MH/NIMH NIH HHS/United States
GR  - R01 MH079079-03/MH/NIMH NIH HHS/United States
GR  - R01CA129541/CA/NCI NIH HHS/United States
GR  - R01 MH079079-05/MH/NIMH NIH HHS/United States
GR  - P01 CA096832-01A10003/CA/NCI NIH HHS/United States
GR  - R01 MH079079-01A2/MH/NIMH NIH HHS/United States
GR  - P01 CA096832/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081217
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (AC133 Antigen)
RN  - 0 (Antigens, CD)
RN  - 0 (Biomarkers)
RN  - 0 (CTNNB1 protein, mouse)
RN  - 0 (Glycoproteins)
RN  - 0 (Lgr5 protein, mouse)
RN  - 0 (PROM1 protein, human)
RN  - 0 (Peptides)
RN  - 0 (Prom1 protein, mouse)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
SB  - IM
CIN - Cancer Cell. 2009 Feb 3;15(2):87-9. doi: 10.1016/j.ccr.2009.01.011. PMID: 
      19185843
MH  - AC133 Antigen
MH  - Adenoma/genetics/metabolism/pathology
MH  - Animals
MH  - Antigens, CD/analysis/genetics/*metabolism
MH  - Biomarkers/analysis/metabolism
MH  - *Cell Lineage
MH  - *Cell Transformation, Neoplastic
MH  - Cells, Cultured
MH  - Genes, Reporter/genetics
MH  - Glycoproteins/analysis/genetics/*metabolism
MH  - Intestinal Neoplasms/genetics/metabolism/pathology
MH  - Intestine, Small/*cytology/pathology
MH  - Mice
MH  - Mutation
MH  - Neoplasm Transplantation
MH  - Neoplastic Stem Cells/cytology/*metabolism/pathology
MH  - Peptides/analysis/genetics/*metabolism
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - Stem Cells/cytology/*metabolism/*pathology
MH  - Transplantation, Heterologous
MH  - Wnt Proteins/metabolism
MH  - beta Catenin/genetics/metabolism
PMC - PMC2633030
MID - NIHMS75275
EDAT- 2008/12/19 09:00
MHDA- 2009/03/12 09:00
PMCR- 2009/07/28
CRDT- 2008/12/19 09:00
PHST- 2008/05/26 00:00 [received]
PHST- 2008/10/20 00:00 [accepted]
PHST- 2008/12/19 09:00 [entrez]
PHST- 2008/12/19 09:00 [pubmed]
PHST- 2009/03/12 09:00 [medline]
PHST- 2009/07/28 00:00 [pmc-release]
AID - nature07589 [pii]
AID - 10.1038/nature07589 [doi]
PST - ppublish
SO  - Nature. 2009 Jan 29;457(7229):603-7. doi: 10.1038/nature07589. Epub 2008 Dec 17.