RGD Reference Report - Expression of vascular endothelial growth factor receptors in human prostate cancer. - Rat Genome Database

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Expression of vascular endothelial growth factor receptors in human prostate cancer.

Authors: Ferrer, FA  Miller, LJ  Lindquist, R  Kowalczyk, P  Laudone, VP  Albertsen, PC  Kreutzer, DL 
Citation: Ferrer FA, etal., Urology. 1999 Sep;54(3):567-72.
RGD ID: 2289936
Pubmed: PMID:10475375   (View Abstract at PubMed)

OBJECTIVES: We recently reported the expression and cytokine regulation of vascular endothelial growth factor (VEGF) in human prostate cancer (PCa). VEGF exerts its angiogenic and pro-tumorigenic properties by way of two high affinity receptors, fms-like tyrosine kinase 1 (FLT-1) and fetal liver kinase 1 (FLK-1). We hypothesized that these receptors are expressed and control VEGF functions in the PCa microenvironment. Herein, we evaluate the expression of these receptors in ex vivo PCa tissue, benign prostatic hypertrophy (BPH) tissue, and cultured PCa cell lines. METHODS: Ex vivo PCa specimens were obtained from patients undergoing radical retropubic prostatectomy. Specimens were selected to contain both PCa and BPH tissue (n = 15). Immunohistochemical analysis using antihuman FLT-1 and FLK-1 was performed and specimens were analyzed to characterize the expression and distribution of both receptors. Immunocytochemical analysis for FLT-1 and FLK-1 was also performed on cultured PCa cell lines (DU-145 and LNCaP). RESULTS: PCa cells expressed the VEGF receptor FLT-1 in 100% of specimens evaluated. Expression of FLK-1 was variable and related to tumor grade; high-grade tumors displayed little or no FLK-1 expression. Vascular endothelial cells (VECs) within areas of PCa consistently expressed both FLT-1 and FLK-1 receptors. FLT-1 and FLK-1 were both expressed in BPH tissue. FLT-1 was expressed in the glandular epithelial cells in BPH, but in most cases FLK-1 was localized specifically to the basal cell layer of hypertrophic glands. FLT-1, but not FLK-1, was expressed by the DU-145 and LNCaP cell lines. CONCLUSIONS: Although they are differentially expressed, both FLT-1 and FLK-1 are present in PCa and BPH. Expression of receptors on VECs of tumor vessels supports the well-established role of VEGF in paracrine stimulation of VECs in the tumor microenvironment. The expression of FLT-1 and FLK-1 on tumor cells themselves suggests a potential autocrine function for VEGF (such as regulating tumor cell proliferation). These findings imply that a novel dual role may exist for VEGF, such that it is involved in tumor cell activation (autocrine), in addition to paracrine actions whereby it regulates endothelial cell functions and subsequent neovascular development.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Prostatic Neoplasms  IEP 2289936protein:increased expression:prostate:expression in 15/15 (100%) of tumors examined and levels increased in neoplastic tissue relative to adjacent benign tissueRGD 
Prostatic Neoplasms  ISOFLT1 (Homo sapiens)2289936; 2289936 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Flt1  (Fms related receptor tyrosine kinase 1)

Genes (Mus musculus)
Flt1  (FMS-like tyrosine kinase 1)

Genes (Homo sapiens)
FLT1  (fms related receptor tyrosine kinase 1)


Additional Information