Overexpression of Id-1 in prostate cancer cells promotes angiogenesis through the activation of vascular endothelial growth factor (VEGF)
Autor: | Tracy C.M. Lau, Qi Wang, Yong-Chuan Wong, Chee Wai Chua, WK Kwok, Ming-Tat Ling, Xianghong Wang, Chun Zhou |
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Rok vydání: | 2005 |
Předmět: |
Inhibitor of Differentiation Protein 1
Male Vascular Endothelial Growth Factor A Cancer Research medicine.medical_specialty Umbilical Veins Angiogenesis Adenocarcinoma Transfection chemistry.chemical_compound Prostate cancer Downregulation and upregulation Internal medicine Cell Line Tumor medicine Humans Neoplasm Metastasis Autocrine signalling Cells Cultured Neovascularization Pathologic business.industry Reverse Transcriptase Polymerase Chain Reaction Cancer Prostatic Neoplasms General Medicine medicine.disease Vascular endothelial growth factor Gene Expression Regulation Neoplastic Repressor Proteins Vascular endothelial growth factor A HIF1A Endocrinology chemistry Cancer research Endothelium Vascular business Transcription Factors |
Zdroj: | Carcinogenesis. 26(10) |
ISSN: | 0143-3334 |
Popis: | Androgen-independent metastatic prostate cancer is the main cause of cancer related death in men. One of the reasons for this is the lack of understanding of the molecular mechanisms leading to the metastatic progression of prostate cancer. In this study, we have demonstrated that overexpression of Id-1 (inhibitor of differentiation/DNA synthesis), a member of the helix–loop–helix family proteins, is a key factor in promoting angiogenesis through activation of the vascular endothelial growth factor (VEGF) in prostate cancer cells. Using prostate cancer cells ectopically transfected with the Id-1 gene, we found that upregulation of Id-1 induced VEGF secretion through activation of the VEGF gene transcription. Downregulation of Id-1, however, led to the suppression of VEGF secretion and its gene promoter activity. The association between Id-1 and VEGF was also confirmed on human xenografts by immunohistochemical staining. In addition, the growth medium generated by the Id-1 expressing cells was able to promote morphological changes as well as capillary tube formation in human umbilical vein endothelial cells (HUVECs) at similar degrees to the recombinant human VEGF. Furthermore, inhibition of VEGF function by the treatment with an Flk-1 inhibitor, SU1498, or with the VEGF neutralizing antibody resulted in the reverse of the angiogenic effect on HUVECs. Our results suggest that overexpression of Id-1 in prostate cancer cells may provide an autocrine signal to promote angiogenesis through the activation of VEGF. Since increased Id-1 has been reported in many types of advanced human cancers, our results indicate that downregulation of Id-1 may be a novel target to inhibit the growth of metastatic cancers through the suppression of angiogenesis. |
Databáze: | OpenAIRE |
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