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Article: Coexpression of hepatocyte growth factor-Met: An early step in ovarian carcinogenesis?

TitleCoexpression of hepatocyte growth factor-Met: An early step in ovarian carcinogenesis?
Authors
Issue Date2001
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2001, v. 20 n. 11, p. 1318-1328 How to Cite?
AbstractSince 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.
Persistent Identifierhttp://hdl.handle.net/10722/178759
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, ASTen_US
dc.contributor.authorPelech, SLen_US
dc.contributor.authorWoo, MMMen_US
dc.contributor.authorYim, Gen_US
dc.contributor.authorRosen, Ben_US
dc.contributor.authorEhlen, Ten_US
dc.contributor.authorLeung, PCKen_US
dc.contributor.authorAuersperg, Nen_US
dc.date.accessioned2012-12-19T09:49:34Z-
dc.date.available2012-12-19T09:49:34Z-
dc.date.issued2001en_US
dc.identifier.citationOncogene, 2001, v. 20 n. 11, p. 1318-1328en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/178759-
dc.description.abstractSince 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.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_US
dc.relation.ispartofOncogeneen_US
dc.subject.meshAutocrine Communicationen_US
dc.subject.meshCell Movementen_US
dc.subject.meshCell Transformation, Neoplasticen_US
dc.subject.meshEpithelial Cells - Cytologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGenetic Predisposition To Diseaseen_US
dc.subject.meshHepatocyte Growth Factor - Biosynthesisen_US
dc.subject.meshHumansen_US
dc.subject.meshMorphogenesisen_US
dc.subject.meshOvarian Neoplasms - Etiology - Geneticsen_US
dc.subject.meshProto-Oncogene Proteins C-Met - Biosynthesisen_US
dc.titleCoexpression of hepatocyte growth factor-Met: An early step in ovarian carcinogenesis?en_US
dc.typeArticleen_US
dc.identifier.emailWong, AST: awong1@hkucc.hku.hken_US
dc.identifier.authorityWong, AST=rp00805en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.onc.1204253en_US
dc.identifier.pmid11313876-
dc.identifier.scopuseid_2-s2.0-0035868390en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035868390&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume20en_US
dc.identifier.issue11en_US
dc.identifier.spage1318en_US
dc.identifier.epage1328en_US
dc.identifier.isiWOS:000167495000006-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridWong, AST=23987963300en_US
dc.identifier.scopusauthoridPelech, SL=19435899100en_US
dc.identifier.scopusauthoridWoo, MMM=7201527679en_US
dc.identifier.scopusauthoridYim, G=36891499900en_US
dc.identifier.scopusauthoridRosen, B=24290886900en_US
dc.identifier.scopusauthoridEhlen, T=6603203782en_US
dc.identifier.scopusauthoridLeung, PCK=12782513900en_US
dc.identifier.scopusauthoridAuersperg, N=7006582556en_US

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