PMID- 10597250
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20181130
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 47
DP  - 1999 Nov 11
TI  - LOT1 is a growth suppressor gene down-regulated by the epidermal growth factor
      receptor ligands and encodes a nuclear zinc-finger protein.
PG  - 6477-87
AB  - We previously reported cloning the rLot1 gene, and its human homolog (hLOT1),
      through analysis of differential gene expression in normal and malignant rat
      ovarian surface epithelial cells. Both human and rat ovarian carcinoma cell lines
      exhibited lost or decreased expression of this gene. Interestingly, the LOT1 gene
      localized at band q25 of human chromosome 6 which is a frequent site for LOH in
      many solid tumors including ovarian cancer. In this report we have further
      characterized the potential role of LOT1 in malignant transformation and
      developed evidence that the gene is a novel target of growth factor signaling
      pathway. Assays using transient transfections showed that LOT1 is a nuclear
      protein and may act as a transcription factor. In vitro and in vivo studies
      involving ovarian cancer cell lines revealed that expression of LOT1 is directly 
      associated with inhibition of cellular proliferation and induction of
      morphological transformations. Additionally, we show that in normal rat ovarian
      surface epithelial cells Lot1 gene expression is responsive to growth factor
      stimulation. Its mRNA is strongly down-regulated by epidermal growth factor
      receptor (EGFR) ligands, namely EGF and TGF-alpha. Blocking the ligand-activated 
      EGFR signal transduction pathway by the specific EGF receptor inhibitor,
      tyrphostin AG1478, and the MEK inhibitor, PD098059, restores the normal level of 
      Lot1 gene expression. It appears that the regulation of Lot1 gene is unique to
      these ligands, as well as the growth promoting agent TPA, since other factors
      either did not affect Lot1 expression, or the effect was modest and transient.
      Altogether, the results suggest that Lot1 expression is primarily mediated via
      EGF receptor or a related pathway and it may regulate the growth promoting
      signals as a zinc-finger motif containing nuclear transcription factor.
FAU - Abdollahi, A
AU  - Abdollahi A
AD  - Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia,
      Pennsylvannia, PA 19111, USA.
FAU - Bao, R
AU  - Bao R
FAU - Hamilton, T C
AU  - Hamilton TC
LA  - eng
GR  - CA56916/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Ligands)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PLAGL1 protein, human)
RN  - 0 (Plagl1 protein, mouse)
RN  - 0 (Plagl1 protein, rat)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Base Sequence
MH  - *Cell Cycle Proteins
MH  - Cell Division
MH  - Cell Line, Transformed
MH  - DNA Primers
MH  - DNA-Binding Proteins/*genetics
MH  - *Down-Regulation
MH  - ErbB Receptors/*metabolism
MH  - *Genes, Suppressor
MH  - *Genes, Tumor Suppressor
MH  - Humans
MH  - Ligands
MH  - Mice
MH  - Nuclear Proteins/genetics
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Signal Transduction
MH  - *Transcription Factors
MH  - Tumor Suppressor Proteins
MH  - *Zinc Fingers
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1038/sj.onc.1203067 [doi]
PST - ppublish
SO  - Oncogene. 1999 Nov 11;18(47):6477-87. doi: 10.1038/sj.onc.1203067.