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Article: Co-expression of vascular endothelial growth factor (VEGF) and its receptors (flk-1 and flt-1) in hormone- induced mammary cancer in the Noble rat

TitleCo-expression of vascular endothelial growth factor (VEGF) and its receptors (flk-1 and flt-1) in hormone- induced mammary cancer in the Noble rat
Authors
Issue Date1999
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjc
Citation
British Journal Of Cancer, 1999, v. 81 n. 8, p. 1335-1343 How to Cite?
AbstractVascular endothelial growth factor (VEGF) is recognized to play a predominant role in breast cancer prognosis. The action of VEGF is mediated by two high-affinity receptors with ligand-stimulated tyrosine kinase activity VEGFR-1/flt-1 and VEGFR-2/flt-1, which are expressed mainly in vascular endothelial cells. To the best of our knowledge, no previous studies on the expression of these receptors in breast cancer cells has been made. We have established a new animal model for breast cancer, using a combination of 17β-oestradiol and testosterone as 'carcinogens'. Taking advantage of the animal model, we have demonstrated that mammary cancer cells expressed not only high levels of VEGF but also, surprisingly, its receptors (flt-1 and flk-1) in mammary cancer cells, intense reactivities to VEGF, flt-1 and flk-1 were observed in mammary cancer cells, especially in invasive mammary carcinoma. Western blot analysis confirmed the increase in flk-1 and flt-1 proteins in induced mammary cancers. Based on these observations, we hypothesize that in mammary cancer, VEGF regulates. In addition to endothelial proliferation and angiogenesis, also growth of cancer cells by an autocrine mechanism mediated through its receptors. To further verify this hypothesis, we investigated the correlation between cellular proliferation and the expression of VEGF, flt-1 and flk-1. Using double-labelling immunocytochemistry, we have shown a correlation between high VEGF activity and Ki-67 expression. The Ki-67 indices in the areas of strong and weak VEGF reactivities were 58.3% and 3.7% respectively. Similarly, there was also a correlation of strong flk-1 and Ki-67 reactivity. The Ki-67 indices for areas of strong and weak flk-1 reactivities were 53.9% and 3.1% respectively. On the other hand, there was a reverse correlation between flt-1 and Ki-67 activities. These results indicate that overexpression of VEGF and flk-1 is correlated with high Ki-67 index. The data, therefore, suggest that VEGF may act as an autocrine growth factor for mammary cancer cells in vivo and this autocrine regulatory role may be mediated through flk-1. The present study is the first report showing that VEGF may act as a growth stimulator for mammary cancer cells.
Persistent Identifierhttp://hdl.handle.net/10722/149576
ISSN
2015 Impact Factor: 5.569
2015 SCImago Journal Rankings: 2.939
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorXie, Ben_US
dc.contributor.authorTam, NNCen_US
dc.contributor.authorTsao, SWen_US
dc.contributor.authorWong, YCen_US
dc.date.accessioned2012-06-26T05:55:28Z-
dc.date.available2012-06-26T05:55:28Z-
dc.date.issued1999en_US
dc.identifier.citationBritish Journal Of Cancer, 1999, v. 81 n. 8, p. 1335-1343en_US
dc.identifier.issn0007-0920en_US
dc.identifier.urihttp://hdl.handle.net/10722/149576-
dc.description.abstractVascular endothelial growth factor (VEGF) is recognized to play a predominant role in breast cancer prognosis. The action of VEGF is mediated by two high-affinity receptors with ligand-stimulated tyrosine kinase activity VEGFR-1/flt-1 and VEGFR-2/flt-1, which are expressed mainly in vascular endothelial cells. To the best of our knowledge, no previous studies on the expression of these receptors in breast cancer cells has been made. We have established a new animal model for breast cancer, using a combination of 17β-oestradiol and testosterone as 'carcinogens'. Taking advantage of the animal model, we have demonstrated that mammary cancer cells expressed not only high levels of VEGF but also, surprisingly, its receptors (flt-1 and flk-1) in mammary cancer cells, intense reactivities to VEGF, flt-1 and flk-1 were observed in mammary cancer cells, especially in invasive mammary carcinoma. Western blot analysis confirmed the increase in flk-1 and flt-1 proteins in induced mammary cancers. Based on these observations, we hypothesize that in mammary cancer, VEGF regulates. In addition to endothelial proliferation and angiogenesis, also growth of cancer cells by an autocrine mechanism mediated through its receptors. To further verify this hypothesis, we investigated the correlation between cellular proliferation and the expression of VEGF, flt-1 and flk-1. Using double-labelling immunocytochemistry, we have shown a correlation between high VEGF activity and Ki-67 expression. The Ki-67 indices in the areas of strong and weak VEGF reactivities were 58.3% and 3.7% respectively. Similarly, there was also a correlation of strong flk-1 and Ki-67 reactivity. The Ki-67 indices for areas of strong and weak flk-1 reactivities were 53.9% and 3.1% respectively. On the other hand, there was a reverse correlation between flt-1 and Ki-67 activities. These results indicate that overexpression of VEGF and flk-1 is correlated with high Ki-67 index. The data, therefore, suggest that VEGF may act as an autocrine growth factor for mammary cancer cells in vivo and this autocrine regulatory role may be mediated through flk-1. The present study is the first report showing that VEGF may act as a growth stimulator for mammary cancer cells.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/bjcen_US
dc.relation.ispartofBritish Journal of Canceren_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshEndothelial Growth Factors - Metabolismen_US
dc.subject.meshKi-67 Antigen - Metabolismen_US
dc.subject.meshLymphokines - Metabolismen_US
dc.subject.meshMammary Neoplasms, Experimental - Metabolismen_US
dc.subject.meshNeoplasms, Hormone-Dependent - Metabolismen_US
dc.subject.meshProto-Oncogene Proteins - Metabolismen_US
dc.subject.meshRatsen_US
dc.subject.meshReceptor Protein-Tyrosine Kinases - Metabolismen_US
dc.subject.meshReceptors, Growth Factor - Metabolismen_US
dc.subject.meshReceptors, Vascular Endothelial Growth Factoren_US
dc.subject.meshVascular Endothelial Growth Factor Aen_US
dc.subject.meshVascular Endothelial Growth Factor Receptor-1en_US
dc.subject.meshVascular Endothelial Growth Factorsen_US
dc.titleCo-expression of vascular endothelial growth factor (VEGF) and its receptors (flk-1 and flt-1) in hormone- induced mammary cancer in the Noble raten_US
dc.typeArticleen_US
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_US
dc.identifier.emailWong, YC:ycwong@hkucc.hku.hken_US
dc.identifier.authorityTsao, SW=rp00399en_US
dc.identifier.authorityWong, YC=rp00316en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.pmid10604730-
dc.identifier.pmcidPMC2362981-
dc.identifier.scopuseid_2-s2.0-0032713067en_US
dc.identifier.hkuros47804-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032713067&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume81en_US
dc.identifier.issue8en_US
dc.identifier.spage1335en_US
dc.identifier.epage1343en_US
dc.identifier.isiWOS:000084036300010-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridXie, B=7201872727en_US
dc.identifier.scopusauthoridTam, NNC=7101712624en_US
dc.identifier.scopusauthoridTsao, SW=7102813116en_US
dc.identifier.scopusauthoridWong, YC=7403041798en_US

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