BIOMAT Database Logo BIOMAT Database Logo

Coexpression of hepatocyte growth factor-Met: an early step in ovarian carcinogenesis? 2001

A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, B.C., Canada V6H 3V5.

Since autocrine regulation of HGF-Met is implicated in many forms of human cancer, we investigated whether the predisposition to develop ovarian cancer in women with hereditary ovarian cancer syndromes involves changes in the expression of HGF-Met by the tissue of origin of epithelial ovarian cancers, the ovarian surface epithelium (OSE). We compared cultures of normal OSE from women with (FH-OSE) (n=20) and with no (NFH-OSE) (n=48) family histories of ovarian cancer, SV40 Tag immortalized OSE lines (IOSE, n=5) and ovarian cancer cell lines (n=3). Cultures derived from 21/22 women with NFH-OSE and 13/13 women with FH-OSE expressed Met mRNA initially. After two to three passages, Met was downregulated in 37% of NFH-OSE cultures but persisted in 100% of FH-OSE cultures and ovarian cancer lines, like other epithelial differentiation markers that are stabilized in FH-OSE and neoplasia. HGF and Met mRNA were concomitantly expressed by NFH-OSE from only three of 32 women but in FH-OSE from eight of 13 women, and also in five of five IOSE and two of three ovarian cancer lines. Conditioned media from FH-OSE, but not NFH-OSE, contained immunoreactive HGF and induced cohort migration which was inhibited by neutralizing HGF antibody. Several signaling molecules of the PI3K pathway, including Akt2 and p70 S6K, were constitutively activated in FH-OSE from six of six women but in NFH-OSE from only four of eight women. Exogenous HGF was mitogenic in OSE, and that effect was regulated through the MAP kinase (ERK1/ERK2) and FRAP/p70 S6K pathways. The proliferative response to HGF was greater in NFH-OSE than in FH-OSE cultures. The results show that FH-OSE cultures differ from NFH-OSE by increased stability of Met expression and by HGF secretion. Constitutive phosphorylation of kinases and a diminished growth response to HGF suggest the presence of autocrine regulation in FH-OSE. In analogy with other cell types where an autocrine HGF-Met loop has been implicated in tumorigenic transformation, this change in FH-OSE may play a role in the enhanced susceptibility to ovarian carcinogenesis in women with hereditary ovarian cancer syndromes.

UI MeSH Term Description Entries
D009024 Morphogenesis The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017228 Hepatocyte Growth Factor Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET. Hepatopoietin,Hepatopoietin A,Scatter Factor,Factor, Hepatocyte Growth,Factor, Scatter,Growth Factor, Hepatocyte
D019859 Proto-Oncogene Proteins c-met Cell surface protein-tyrosine kinase receptors for HEPATOCYTE GROWTH FACTOR. They consist of an extracellular alpha chain which is disulfide-linked to the transmembrane beta chain. The cytoplasmic portion contains the catalytic domain and sites critical for the regulation of kinase activity. Mutations in the c-met proto-oncogene are associated with papillary renal carcinoma and other neoplasia. HGF Receptor,Hepatocyte Growth Factor Receptor,c-met Proteins,met Proto-Oncogene Proteins,MET Proto-Oncogene, Receptor Tyrosine Kinase,MET Receptor Tyrosine Kinase,Receptor, HGF,Receptor, Hepatocyte Growth Factor,Receptor, Scatter Factor,Scatter Factor Receptor,c-Met Receptor Tyrosine Kinase,MET Proto Oncogene, Receptor Tyrosine Kinase,Proto Oncogene Proteins c met,Proto-Oncogene Proteins, met,c Met Receptor Tyrosine Kinase,c met Proteins,met Proto Oncogene Proteins
D019898 Autocrine Communication Mode of communication wherein a bound hormone affects the function of the cell type that produced the hormone. Autocrine Signaling,Autocrine Communications,Autocrine Signalings,Communication, Autocrine,Communications, Autocrine,Signaling, Autocrine,Signalings, Autocrine

Related Publications

A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
Coexpression of hepatocyte growth factor and receptor (Met) in human breast carcinoma.
January 1996, The American journal of pathology,
A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
Hepatocyte growth factor and Met receptor expression in human pancreatic carcinogenesis.
October 1995, The American journal of pathology,
A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
Coexpression of hepatocyte growth factor and c-Met proto-oncogene product in synovial sarcoma.
October 1998, Pathology international,
A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
Coexpression of the c-met proto-oncogene and hepatocyte growth factor in human pancreatic cancer.
November 1994, Cancer research,
A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
Coexpression of hepatocyte growth factor and its receptor (c-met oncogene) in HGL4 glioblastoma cells.
January 1996, Oncology,
A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
[Coexpression of hepatocyte growth factor-scatter factor (HGF-SF) and HGF-SF receptors (c-met proto-oncogene) in mammalian brain].
January 1994, Verhandlungen der Deutschen Gesellschaft fur Pathologie,
A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
Hepatocyte growth factor and Met in drug discovery.
May 2015, Journal of biochemistry,
A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
MACC1 induces metastasis in ovarian carcinoma by upregulating hepatocyte growth factor receptor c-MET.
August 2014, Oncology letters,
A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
Hepatocyte growth factor--scatter factor: mitogen, motogen, and met.
June 1991, Cancer cells (Cold Spring Harbor, N.Y. : 1989),
A S Wong, and S L Pelech, and M M Woo, and G Yim, and B Rosen, and T Ehlen, and P C Leung, and N Auersperg
Hepatocyte growth factor and c-Met/hepatocyte growth factor receptor in pulmonary adenocarcinomas: an evaluation of their expression as prognostic markers.
January 1996, Oncology,
Copied contents to your clipboard!