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Article: Aberrant expression of hepatocyte growth factor and its receptor, c-Met, during sex hormone-induced prostatic carcinogenesis in the Noble rat

TitleAberrant expression of hepatocyte growth factor and its receptor, c-Met, during sex hormone-induced prostatic carcinogenesis in the Noble rat
Authors
Issue Date2000
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2000, v. 21 n. 12, p. 2183-2191 How to Cite?
AbstractHepatocyte growth factor (HGF) is a multifunctional cytokine which acts as a mitogen, motogen, morphogen and angiogenic factor of epithelial cells. HGF receptor is encoded by a proto-oncogene, c-met, which is overexpressed in various cancers. The role of HGF and c-Met in prostate carcinogenesis, especially in the early stages, is undefined. In this study, prostatic dysplasia and carcinomas were induced by testosterone propionate and 17β-estradiol in Noble rats. The expression of HGF and c-Met was assessed at a protein level by immunohistochemistry and western blot analysis. Intense immunostaining for HGFα and c-Met β-chain was co-localized in dysplastic lesions and in primary and metastatic cancer cells. The levels of HGFα expression were similar among normal control, dysplastic and cancerous prostate tissues, as determined by western blot analysis. Immunoblot study for c-Met under reducing conditions identified two bands at 145 kDa (β-subunit of c-Met) and 170 kDa (precursor form of c-Met) in rat liver extracts. However, two bands at Ο220 and 245 kDa were detected in hormone-treated dysplastic prostate tissues and primary tumors. Overexpression of the 220 kDa band was observed in long-term (10-12 months) hormone-treated prostate and primary tumor extracts. Metastatic tumors consistently exhibited up-regulation of a single 245 kDa band. Under non-reducing conditions, however, protein bands of 220, 280 or 300 kDa were seen in the blots. The hormone-treated prostate tissues and metastatic tumors expressed the 220 and 300 kDa proteins, respectively. The majority of primary tumors expressed the 280 kDa protein. In summary, HGF and its receptor, c-Met, were co-expressed in dysplastic and tumor cells, suggesting that an autocrine mode of action may be involved in prostate carcinogenesis. The close correlation of expression of the high-molecular-weight isoforms of c-Met with different stages of carcinogenesis implicates that they might play differential roles in the onset, progression, growth and metastasis in prostate cancer.
Persistent Identifierhttp://hdl.handle.net/10722/67656
ISSN
2014 Impact Factor: 5.334
2014 SCImago Journal Rankings: 2.152
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTam, NNCen_HK
dc.contributor.authorChung, SSMen_HK
dc.contributor.authorLee, DTWen_HK
dc.contributor.authorWong, YCen_HK
dc.date.accessioned2010-09-06T05:57:05Z-
dc.date.available2010-09-06T05:57:05Z-
dc.date.issued2000en_HK
dc.identifier.citationCarcinogenesis, 2000, v. 21 n. 12, p. 2183-2191en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67656-
dc.description.abstractHepatocyte growth factor (HGF) is a multifunctional cytokine which acts as a mitogen, motogen, morphogen and angiogenic factor of epithelial cells. HGF receptor is encoded by a proto-oncogene, c-met, which is overexpressed in various cancers. The role of HGF and c-Met in prostate carcinogenesis, especially in the early stages, is undefined. In this study, prostatic dysplasia and carcinomas were induced by testosterone propionate and 17β-estradiol in Noble rats. The expression of HGF and c-Met was assessed at a protein level by immunohistochemistry and western blot analysis. Intense immunostaining for HGFα and c-Met β-chain was co-localized in dysplastic lesions and in primary and metastatic cancer cells. The levels of HGFα expression were similar among normal control, dysplastic and cancerous prostate tissues, as determined by western blot analysis. Immunoblot study for c-Met under reducing conditions identified two bands at 145 kDa (β-subunit of c-Met) and 170 kDa (precursor form of c-Met) in rat liver extracts. However, two bands at Ο220 and 245 kDa were detected in hormone-treated dysplastic prostate tissues and primary tumors. Overexpression of the 220 kDa band was observed in long-term (10-12 months) hormone-treated prostate and primary tumor extracts. Metastatic tumors consistently exhibited up-regulation of a single 245 kDa band. Under non-reducing conditions, however, protein bands of 220, 280 or 300 kDa were seen in the blots. The hormone-treated prostate tissues and metastatic tumors expressed the 220 and 300 kDa proteins, respectively. The majority of primary tumors expressed the 280 kDa protein. In summary, HGF and its receptor, c-Met, were co-expressed in dysplastic and tumor cells, suggesting that an autocrine mode of action may be involved in prostate carcinogenesis. The close correlation of expression of the high-molecular-weight isoforms of c-Met with different stages of carcinogenesis implicates that they might play differential roles in the onset, progression, growth and metastasis in prostate cancer.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.rightsCarcinogenesis. Copyright © Oxford University Press.en_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshHepatocyte Growth Factor - analysis - geneticsen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMolecular Weighten_HK
dc.subject.meshNeoplasm Metastasisen_HK
dc.subject.meshPrecancerous Conditions - chemically induced - genetics - pathologyen_HK
dc.subject.meshProstate - drug effects - metabolism - pathologyen_HK
dc.subject.meshProstatic Neoplasms - chemically induced - genetics - pathologyen_HK
dc.subject.meshProtein Subunitsen_HK
dc.subject.meshProto-Oncogene Proteins c-met - analysis - geneticsen_HK
dc.subject.meshRatsen_HK
dc.subject.meshRats, Inbred Strainsen_HK
dc.subject.meshTestosterone - toxicityen_HK
dc.subject.meshTime Factorsen_HK
dc.titleAberrant expression of hepatocyte growth factor and its receptor, c-Met, during sex hormone-induced prostatic carcinogenesis in the Noble raten_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0143-3334&volume=21&issue=12&spage=2183&epage=2191&date=2000&atitle=Aberrant+expression+of+hepatocyte+growth+factor+and+its+receptor,+c-Met,+during+sex+hormone-induced+prostatic+carcinogenesis+in+the+Noble+raten_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hken_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid11133807en_HK
dc.identifier.scopuseid_2-s2.0-0034526646en_HK
dc.identifier.hkuros56508en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034526646&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume21en_HK
dc.identifier.issue12en_HK
dc.identifier.spage2183en_HK
dc.identifier.epage2191en_HK
dc.identifier.isiWOS:000166347100007-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridTam, NNC=7101712624en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK
dc.identifier.scopusauthoridLee, DTW=7406666118en_HK
dc.identifier.scopusauthoridWong, YC=7403041798en_HK

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