PMID- 10340382
OWN - NLM
STAT- MEDLINE
DCOM- 19990608
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 20
DP  - 1999 May 20
TI  - Disabled-2 inactivation is an early step in ovarian tumorigenicity.
PG  - 3104-13
AB  - Disabled-2 (Dab2) functions in mitogenic signal transduction pathway, and is
      frequently activated by homozygous gene deletion in tumors, suggesting that Dab2 
      is a candidate tumor suppressor. Here, we surveyed the expression of Dab2, and
      report that Dab2 is expressed in a variety of tissues, and the level of
      expression is particularly high in ovary and breast. Dab2 expression was also
      detected in immortalized breast and ovarian epithelial cells. However, in more
      than a dozen established tumor cell lines derived from breast and ovarian
      epithelial tumors examined by Western blotting, Dab2 expression was undetectable 
      in 90% of these cell lines. Histological staining of human ovarian tissues with
      specific anti-Dab2 antibodies indicated that Dab2 is highly expressed in the
      surface epithelial layer. In an immunohistological study of 26 ovarian
      carcinomas, 22 (85%) of the tumors were found to lose the expression of Dab2 in
      the tumor cells, which are epithelial origin. Loss of Dab2 expression is not
      correlated with tumor grade, suggesting that Dab2 is lost in an early stage of
      tumorigenicity. Indeed, loss of Dab2 correlates closely with morphological
      transformation of the surface epithelial cells. Additionally, loss of Dab2
      protein occurs in hyperproliferative, but histological benign ovarian epithelium,
      suggesting that loss of Dab2 occurs in pre-malignant lesions. Thus, this study
      indicates that the loss of Dab2 expression is correlated with tumorigenicity of
      the cells disregarding the grade of the tumors, and loss of Dab2 expression is an
      early event in ovarian malignancies.
FAU - Fazili, Z
AU  - Fazili Z
AD  - Department of Biochemistry and Winship Cancer Center, Emory University School of 
      Medicine, Atlanta, Georgia 30322, USA.
FAU - Sun, W
AU  - Sun W
FAU - Mittelstaedt, S
AU  - Mittelstaedt S
FAU - Cohen, C
AU  - Cohen C
FAU - Xu, X X
AU  - Xu XX
LA  - eng
GR  - R01 CA75389/CA/NCI NIH HHS/United States
GR  - R55 CA70783/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 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (DAB2 protein, human)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Amino Acid Sequence
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Breast Neoplasms/genetics/pathology
MH  - Cell Transformation, Neoplastic/genetics
MH  - Epithelial Cells/pathology
MH  - Female
MH  - Genes, Tumor Suppressor
MH  - Humans
MH  - Molecular Sequence Data
MH  - Ovarian Neoplasms/genetics/*pathology
MH  - Ovary/pathology
MH  - Phosphoproteins/chemistry/*genetics/metabolism
MH  - *Proteins
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Proteins
EDAT- 1999/05/26 00:00
MHDA- 1999/05/26 00:01
CRDT- 1999/05/26 00:00
PHST- 1999/05/26 00:00 [pubmed]
PHST- 1999/05/26 00:01 [medline]
PHST- 1999/05/26 00:00 [entrez]
AID - 10.1038/sj.onc.1202649 [doi]
PST - ppublish
SO  - Oncogene. 1999 May 20;18(20):3104-13. doi: 10.1038/sj.onc.1202649.