PMID- 14568991
OWN - NLM
STAT- MEDLINE
DCOM- 20031203
LR  - 20220408
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 163
IP  - 2
DP  - 2003 Oct 27
TI  - Akt activation disrupts mammary acinar architecture and enhances proliferation in 
      an mTOR-dependent manner.
PG  - 315-26
AB  - Activation of the serine/threonine kinase Akt/PKB positively impacts on three 
      cellular processes relevant to tumor progression: proliferation, survival, and 
      cell size/growth. Using a three-dimensional culture model of MCF-10A mammary 
      cells, we have examined how Akt influences the morphogenesis of polarized 
      epithelial structures. Activation of a conditionally active variant of Akt 
      elicits large, misshapen structures, which primarily arise from the combined 
      effects of Akt on proliferation and cell size. Importantly, Akt activation 
      amplifies proliferation during the early stages of morphogenesis, but cannot 
      overcome signals suppressing proliferation in late-stage cultures. Akt also 
      cooperates with oncoproteins such as cyclin D1 or HPV E7 to promote proliferation 
      and morphogenesis in the absence of growth factors. Pharmacological inhibition of 
      the Akt effector, mammalian target of rapamycin (mTOR), with rapamycin prevents 
      the morphological disruption elicited by Akt activation, including its effect on 
      cell size and number, and the cooperative effect of Akt on oncogene-driven 
      proliferation, indicating that mTOR function is required for the multiple 
      biological effects of Akt activation during morphogenesis.
FAU - Debnath, Jayanta
AU  - Debnath J
AD  - Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
FAU - Walker, Stephanie J
AU  - Walker SJ
FAU - Brugge, Joan S
AU  - Brugge JS
LA  - eng
GR  - P01 CA080111/CA/NCI NIH HHS/United States
GR  - P50 CA089393/CA/NCI NIH HHS/United States
GR  - CA80111/CA/NCI NIH HHS/United States
GR  - CA89393/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031020
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 136601-57-5 (Cyclin D1)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Apoptosis
MH  - Breast/*cytology/drug effects/*metabolism
MH  - Cell Division/drug effects
MH  - Cell Line
MH  - Cell Line, Transformed
MH  - Cell Polarity/drug effects
MH  - Cell Size/drug effects
MH  - Cell Survival/drug effects
MH  - Cyclin D1/metabolism
MH  - DNA/analysis
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Epithelial Cells/cytology/drug effects/metabolism
MH  - Humans
MH  - Morphogenesis/drug effects
MH  - Protein Kinase Inhibitors
MH  - Protein Kinases/drug effects/*metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/genetics/*metabolism/pharmacology
MH  - Proto-Oncogene Proteins c-akt
MH  - Retroviridae/genetics
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
PMC - PMC2173511
EDAT- 2003/10/22 05:00
MHDA- 2003/12/04 05:00
PMCR- 2004/04/27
CRDT- 2003/10/22 05:00
PHST- 2003/10/22 05:00 [pubmed]
PHST- 2003/12/04 05:00 [medline]
PHST- 2003/10/22 05:00 [entrez]
PHST- 2004/04/27 00:00 [pmc-release]
AID - jcb.200304159 [pii]
AID - 200304159 [pii]
AID - 10.1083/jcb.200304159 [doi]
PST - ppublish
SO  - J Cell Biol. 2003 Oct 27;163(2):315-26. doi: 10.1083/jcb.200304159. Epub 2003 Oct 
      20.