PMID- 10394368
OWN - NLM
STAT- MEDLINE
DCOM- 19990716
LR  - 20220224
IS  - 1097-2765 (Print)
IS  - 1097-2765 (Linking)
VI  - 3
IP  - 6
DP  - 1999 Jun
TI  - Loss-of-function mutations in PPAR gamma associated with human colon cancer.
PG  - 799-804
AB  - The gamma isoform of the peroxisome proliferator-activated receptor, PPAR gamma, 
      regulates adipocyte differentiation and has recently been shown to be expressed
      in neoplasia of the colon and other tissues. We have found four somatic PPAR
      gamma mutations among 55 sporadic colon cancers: one nonsense, one frameshift,
      and two missense mutations. Each greatly impaired the function of the protein.
      c.472delA results in deletion of the entire ligand binding domain. Q286P and
      K319X retain a total or partial ligand binding domain but lose the ability to
      activate transcription through a failure to bind to ligands. R288H showed a
      normal response to synthetic ligands but greatly decreased transcription and
      binding when exposed to natural ligands. These data indicate that colon cancer in
      humans is associated with loss-of-function mutations in PPAR gamma.
FAU - Sarraf, P
AU  - Sarraf P
AD  - Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical
      School, Boston, Massachusetts 02115, USA.
FAU - Mueller, E
AU  - Mueller E
FAU - Smith, W M
AU  - Smith WM
FAU - Wright, H M
AU  - Wright HM
FAU - Kum, J B
AU  - Kum JB
FAU - Aaltonen, L A
AU  - Aaltonen LA
FAU - de la Chapelle, A
AU  - de la Chapelle A
FAU - Spiegelman, B M
AU  - Spiegelman BM
FAU - Eng, C
AU  - Eng C
LA  - eng
GR  - P30 CA16058/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  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 0 (Chromans)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Ligands)
RN  - 0 (Linoleic Acids)
RN  - 0 (Linoleic Acids, Conjugated)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Thiazoles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Transcription Factors)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - 15514-85-9 (9-hydroxy-10,12-octadecadienoic acid)
RN  - 60203-57-8 (9-deoxy-delta-9-prostaglandin D2)
RN  - 73945-47-8 (15-hydroxy-5,8,11,13-eicosatetraenoic acid)
RN  - I66ZZ0ZN0E (Troglitazone)
RN  - RXY07S6CZ2 (Prostaglandin D2)
SB  - IM
MH  - Amino Acid Substitution
MH  - Binding Sites
MH  - Chromans/metabolism/pharmacology
MH  - Colorectal Neoplasms/*genetics/metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Dimerization
MH  - Exons/genetics
MH  - Genes, Tumor Suppressor/genetics/physiology
MH  - Humans
MH  - Hydroxyeicosatetraenoic Acids/metabolism
MH  - Ligands
MH  - Linoleic Acids/metabolism
MH  - *Linoleic Acids, Conjugated
MH  - *Mutation
MH  - Prostaglandin D2/analogs & derivatives/metabolism/pharmacology
MH  - Protein Binding
MH  - Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
MH  - Receptors, Retinoic Acid/metabolism
MH  - Response Elements/genetics
MH  - Retinoid X Receptors
MH  - Rosiglitazone
MH  - Thiazoles/metabolism/pharmacology
MH  - *Thiazolidinediones
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcriptional Activation/drug effects
MH  - Troglitazone
EDAT- 1999/07/08 00:00
MHDA- 1999/07/08 00:01
CRDT- 1999/07/08 00:00
PHST- 1999/07/08 00:00 [pubmed]
PHST- 1999/07/08 00:01 [medline]
PHST- 1999/07/08 00:00 [entrez]
AID - S1097-2765(01)80012-5 [pii]
AID - 10.1016/s1097-2765(01)80012-5 [doi]
PST - ppublish
SO  - Mol Cell. 1999 Jun;3(6):799-804. doi: 10.1016/s1097-2765(01)80012-5.