Expression of the VEGF and angiopoietin genes in endometrial atypical hyperplasia and endometrial cancer.
Angiogenesis is critical for the growth and metastasis of endometrial cancer and is therefore an important therapeutic target. Vascular endothelial growth factor-A (VEGF-A) is a key molecule in angiogenesis, but the identification of related molecules and the angiopoietins suggests a more complex picture. We investigated the presence of transcripts for VEGF-A, VEGF-B, VEGF-C, VEGF-D, Angiopoietin-1 and Angiopoietin-2 in benign endometrium, atypical complex hyperplasia (ACH) and endometrioid endometrial carcinoma using in situ hybridisation. We confirmed the presence of VEGF-A mRNA in the epithelial cells of cancers examined (13 out of 13), but not in benign endometrium or ACH. We also demonstrate, using quantitative polymerase chain reaction, that levels of VEGF-B mRNA are significantly lower in endometrial cancer than benign endometrium. We conclude that loss of VEGF-B may contribute to the development of endometrial carcinoma by modulating availability of receptors for VEGF-A.
Holland
C M
CM
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB1 1QP, UK. cath.holland@obgyn.cam.ac.uk
Day
K
K
Evans
A
A
Smith
S K
SK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000096:biosynthesis* / Q000235:genetics; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000235:genetics; D004714:Endometrial Hyperplasia / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000097382:CD68 Molecule
D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D007633:Keratins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C067980:CD68 antigen, human; D000097382:CD68 Molecule