VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.
Angiogenesis, which plays an important role in tumor growth and progression of breast cancer, is regulated by a balance between pro- and anti-angiogenic factors. Expression of vascular endothelial growth factor (VEGF) is up-regulated during hypoxia by hypoxia-inducible factor-1α (HIF-1α). It is know...
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oai:doaj.org-article:ab26d5908b67434d95e177b60285c75f2021-11-18T08:01:52ZVEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer.1932-620310.1371/journal.pone.0053070https://doaj.org/article/ab26d5908b67434d95e177b60285c75f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23326384/?tool=EBIhttps://doaj.org/toc/1932-6203Angiogenesis, which plays an important role in tumor growth and progression of breast cancer, is regulated by a balance between pro- and anti-angiogenic factors. Expression of vascular endothelial growth factor (VEGF) is up-regulated during hypoxia by hypoxia-inducible factor-1α (HIF-1α). It is known that there is an interaction between HIF-1α and BRCA1 carrier cancers, but little has been reported about angiogenesis in BRCA1-2 carrier and BRCAX breast cancers. In this study, we investigated the expression of VEGF and HIF-1α and microvessel density (MVD) in 26 BRCA1-2 carriers and 58 BRCAX compared to 77 sporadic breast cancers, by immunohistochemistry. VEGF expression in BRCA1-2 carriers was higher than in BRCAX cancer tissues (p = 0.0001). Furthermore, VEGF expression was higher in both BRCA1-2 carriers and BRCAX than the sporadic group (p<0.0001). VEGF immunoreactivity was correlated with poor tumor grade (p = 0.0074), hormone receptors negativity (p = 0.0206, p = 0.0002 respectively), and MIB-1-labeling index (p = 0.0044) in familial cancers (BRCA1-2 and BRCAX). The percentage of nuclear HIF-1α expression was higher in the BRCA1-2 carriers than in BRCAX cancers (p<0.05), and in all familial than in sporadic tumor tissues (p = 0.0045). A higher MVD was observed in BRCA1-2 carrier than in BRCAX and sporadic cancer tissues (p = 0.002, p = 0.0001 respectively), and in all familial tumors than in sporadic tumors (p = 0.01). MVD was positively related to HIF-1α expression in BRCA1-2 carriers (r = 0.521, p = 0.006), and, in particular, we observed a highly significant correlation in the familial group (r = 0.421, p<0.0001). Our findings suggest that angiogenesis plays a crucial role in BRCA1-2 carrier breast cancers. Prospective studies in larger BRCA1-2 carrier series are needed to improve the best therapeutic strategies for this subgroup of breast cancer patients.Concetta SaponaroAndrea MalfettoneGirolamo RanieriKatia DanzaGiovanni SimoneAngelo ParadisoAnita MangiaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53070 (2013) |
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Medicine R Science Q Concetta Saponaro Andrea Malfettone Girolamo Ranieri Katia Danza Giovanni Simone Angelo Paradiso Anita Mangia VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer. |
description |
Angiogenesis, which plays an important role in tumor growth and progression of breast cancer, is regulated by a balance between pro- and anti-angiogenic factors. Expression of vascular endothelial growth factor (VEGF) is up-regulated during hypoxia by hypoxia-inducible factor-1α (HIF-1α). It is known that there is an interaction between HIF-1α and BRCA1 carrier cancers, but little has been reported about angiogenesis in BRCA1-2 carrier and BRCAX breast cancers. In this study, we investigated the expression of VEGF and HIF-1α and microvessel density (MVD) in 26 BRCA1-2 carriers and 58 BRCAX compared to 77 sporadic breast cancers, by immunohistochemistry. VEGF expression in BRCA1-2 carriers was higher than in BRCAX cancer tissues (p = 0.0001). Furthermore, VEGF expression was higher in both BRCA1-2 carriers and BRCAX than the sporadic group (p<0.0001). VEGF immunoreactivity was correlated with poor tumor grade (p = 0.0074), hormone receptors negativity (p = 0.0206, p = 0.0002 respectively), and MIB-1-labeling index (p = 0.0044) in familial cancers (BRCA1-2 and BRCAX). The percentage of nuclear HIF-1α expression was higher in the BRCA1-2 carriers than in BRCAX cancers (p<0.05), and in all familial than in sporadic tumor tissues (p = 0.0045). A higher MVD was observed in BRCA1-2 carrier than in BRCAX and sporadic cancer tissues (p = 0.002, p = 0.0001 respectively), and in all familial tumors than in sporadic tumors (p = 0.01). MVD was positively related to HIF-1α expression in BRCA1-2 carriers (r = 0.521, p = 0.006), and, in particular, we observed a highly significant correlation in the familial group (r = 0.421, p<0.0001). Our findings suggest that angiogenesis plays a crucial role in BRCA1-2 carrier breast cancers. Prospective studies in larger BRCA1-2 carrier series are needed to improve the best therapeutic strategies for this subgroup of breast cancer patients. |
format |
article |
author |
Concetta Saponaro Andrea Malfettone Girolamo Ranieri Katia Danza Giovanni Simone Angelo Paradiso Anita Mangia |
author_facet |
Concetta Saponaro Andrea Malfettone Girolamo Ranieri Katia Danza Giovanni Simone Angelo Paradiso Anita Mangia |
author_sort |
Concetta Saponaro |
title |
VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer. |
title_short |
VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer. |
title_full |
VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer. |
title_fullStr |
VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer. |
title_full_unstemmed |
VEGF, HIF-1α expression and MVD as an angiogenic network in familial breast cancer. |
title_sort |
vegf, hif-1α expression and mvd as an angiogenic network in familial breast cancer. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/ab26d5908b67434d95e177b60285c75f |
work_keys_str_mv |
AT concettasaponaro vegfhif1aexpressionandmvdasanangiogenicnetworkinfamilialbreastcancer AT andreamalfettone vegfhif1aexpressionandmvdasanangiogenicnetworkinfamilialbreastcancer AT girolamoranieri vegfhif1aexpressionandmvdasanangiogenicnetworkinfamilialbreastcancer AT katiadanza vegfhif1aexpressionandmvdasanangiogenicnetworkinfamilialbreastcancer AT giovannisimone vegfhif1aexpressionandmvdasanangiogenicnetworkinfamilialbreastcancer AT angeloparadiso vegfhif1aexpressionandmvdasanangiogenicnetworkinfamilialbreastcancer AT anitamangia vegfhif1aexpressionandmvdasanangiogenicnetworkinfamilialbreastcancer |
_version_ |
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