Expression and function of angiopoietin-1 in breast cancer.
Angiopoietin-1 (Ang1) has been shown to act as an angiogenic promoter in embryonic angiogenesis by promoting vascular branching, pericyte recruitment and endothelial survival. We have investigated the role of Ang1 in tumour neovascularization under clinical conditions and in animal models. The expression of Ang1 in clinical breast cancer specimens was analysed by using laser-capture microdissection and reverse transcriptase-linked polymerase chain reaction (RT-PCR) on RNA isolated from the samples. Despite the expression of Ang1 in many human breast cancer cell lines, the gene was expressed in only three of 21 breast cancer clinical specimens, even though its receptor, Tie2, is abundant in the vasculature of all of these tumours. Ang1 was then overexpressed in a human breast cancer cell line (MCF-7) on its own and in conjunction with FGF1, an angiogenic factor shown to be able to increase the tumorigenicity of MCF-7 cells. High concentrations of Ang1 were produced in the conditioned media of the transfected cells (range 156-820 ng ml(-1)). However, in contrast to its physiological role as promoter of angiogenesis, overexpression of Ang1 did not enhance tumour growth, but instead caused up to a 3-fold retardation of tumour growth (P = 0.003).
Hayes
A J
AJ
Department of Oncology, Department of Biostatistics, Georgetown University Medical Center, 3970 Reservoir Road, NW RB/E301, Washington, DC 20007, USA.
Huang
W Q
WQ
Yu
J
J
Maisonpierre
P C
PC
Liu
A
A
Kern
F G
FG
Lippman
M E
ME
McLeskey
S W
SW
Li
L Y
LY
D042683:Angiopoietin-1; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016466:CHO Cells; D002455:Cell Division / Q000235:genetics; D006224:Cricetinae; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1