PMID- 19605689
OWN - NLM
STAT- MEDLINE
DCOM- 20090720
LR  - 20211020
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 23
IP  - 14
DP  - 2009 Jul 15
TI  - Regulation of transgenes in three-dimensional cultures of primary mouse mammary 
      cells demonstrates oncogene dependence and identifies cells that survive 
      deinduction.
PG  - 1677-88
LID - 10.1101/gad.1801809 [doi]
AB  - The advent of targeted therapies for cancer has provoked interest in experimental 
      models for the systematic study of oncogene dependence. To that end, we developed 
      a three-dimensional (3D) culture system to analyze the responses of primary mouse 
      mammary epithelial cells to the induction and deinduction of oncogenes. Mammary 
      cells derived from normal virgin mice, or from tritransgenic mice 
      (TetO-MYC;TetO-Kras(G12D);MMTV-rtTA) in which MYC and mutant Kras can be 
      regulated by doxycycline, develop from single cells into polarized acini. Lumen 
      formation occurs without apparent apoptosis, and the hollow spheres of cells 
      enlarge by division, with metaphase plates oriented perpendicularly to the apical 
      surface. When MYC and Kras(G12D) are induced, the acini enlarge and form solid, 
      depolarized spheres. Upon deinduction of MYC and Kras(G12D) the solid structures 
      regress, leaving a repolarized monolayer of viable cells. These cells display a 
      phenotype consistent with progenitors of mammary epithelium: They exclude Hoechst 
      dye 33342, and reform acini in 3D cultures and repopulate mammary fat pads more 
      efficiently than cells harvested from uninduced acini. Moreover, cells in the 
      surviving spheres retain the ability to respond to reinduction and thus may 
      represent the type of cells that give rise to recurrent tumors.
FAU - Jechlinger, Martin
AU  - Jechlinger M
AD  - Program in Cancer Biology and Genetics, Sloan Kettering Institute, Memorial 
      Sloan-Kettering Cancer Center, New York, New York 10065, USA. jechlinm@mskcc.org
FAU - Podsypanina, Katrina
AU  - Podsypanina K
FAU - Varmus, Harold
AU  - Varmus H
LA  - eng
GR  - P01 CA94060/CA/NCI NIH HHS/United States
GR  - K01 CA118731/CA/NCI NIH HHS/United States
GR  - P01 CA094060/CA/NCI NIH HHS/United States
GR  - R24 CA83084/CA/NCI NIH HHS/United States
GR  - R24 CA083084/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - P30-CA 08748/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Benzimidazoles)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
RN  - N12000U13O (Doxycycline)
RN  - P976261J69 (bisbenzimide ethoxide trihydrochloride)
SB  - IM
CIN - Nat Rev Cancer. 2009 Sep;9(9):613. PMID: 19705530
MH  - Animals
MH  - Anti-Bacterial Agents/pharmacology
MH  - Apoptosis
MH  - Benzimidazoles/metabolism
MH  - Caspase 3/metabolism
MH  - Cell Culture Techniques/*methods
MH  - Cell Division
MH  - Cell Survival/*physiology
MH  - Doxycycline/pharmacology
MH  - Female
MH  - *Gene Expression Regulation/drug effects
MH  - Mammary Glands, Animal/*cytology
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitochondria/metabolism
MH  - Oncogenes/*genetics
MH  - Stem Cells/cytology
MH  - Transcriptional Activation
MH  - Transgenes/*physiology
PMC - PMC2714708
EDAT- 2009/07/17 09:00
MHDA- 2009/07/21 09:00
PMCR- 2010/01/15
CRDT- 2009/07/17 09:00
PHST- 2009/07/17 09:00 [entrez]
PHST- 2009/07/17 09:00 [pubmed]
PHST- 2009/07/21 09:00 [medline]
PHST- 2010/01/15 00:00 [pmc-release]
AID - 23/14/1677 [pii]
AID - 10.1101/gad.1801809 [doi]
PST - ppublish
SO  - Genes Dev. 2009 Jul 15;23(14):1677-88. doi: 10.1101/gad.1801809.