Expression of angiopoietin-1, angiopoietin-2, and Tie2 genes in normal ovary with corpus luteum and in ovarian cancer.
OBJECTIVE
The recent discovery of angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) has provided novel and important insights into the molecular mechanisms of blood vessel formation. Ang1 and Ang2 bind with similar affinity to the endothelial cell tyrosine kinase receptor Tie2. Our purpose was to assess the potential role of the Ang/Tie2 system in physiological and pathological angiogenesis in the ovary.


METHODS
Ang1, Ang2, and Tie2 gene expression in 14 normal ovaries with corpus luteum (CL) and in 19 cases of ovarian cancer were analyzed by polymerase chain reaction of RNA after reverse transcription. The level of each gene expression was presented by the relative yield of each gene to the beta(2)-microglobulin gene, respectively. Furthermore, cellular distribution of Ang1 and Ang2 mRNA was examined by in situ hybridization, and localization of Tie2 was studied by immunochemistry.


RESULTS
The Ang1, Ang2, and Tie2 gene expression in normal ovary with CL ranged from 0.18 to 1.06 (median 0.54), 0.31-2.64 (median 1.01), and 0.10-0.47 (median 0.20), respectively. The expression of these same genes in ovarian cancer ranged from 0.06 to 0.75 (median 0.14), 0.69-1.59 (median 1.12), and 0.04-0.35 (median 0.15), respectively. Ang1 gene expression in normal ovary with CL was significantly higher than that in ovarian cancer (p = 0.0004). The gene expression levels of Ang2 and Tie2 were statistically the same in both groups. There was a significant correlation between Ang1 gene expression and Tie2 gene expression in normal ovary with CL (r = 0.619, p = 0.018). No such significant correlation was found in ovarian cancer. Moreover, Ang2 gene expression showed no significant correlation with the Tie2 gene expression either in normal ovary with CL or in ovarian cancer. Transcripts for Ang1 were observed in CL cells and endothelial cells around CL, and in tumor cells and endothelial cells at the periphery of tumor invasion. Ang2 transcripts were expressed in the same patterns. Tie2 expression was positive primarily in the endothelial cells around CL and in those at the periphery of tumor invasion.


CONCLUSIONS
Our results indicate that there is a difference in the Ang/Tie2 gene expression between physiological and pathological angiogenesis in the ovary. This finding may aid in the development of new therapeutic interventions for ovarian cancer.
Department of Obstetrics and Gynecology, Shimane Medical University, Izumo, Japan. hata31@shimane-med.ac.jp
Kohkichi
K
Hata
Jun
J
Udagawa
Ritsuto
R
Fujiwaki
Kentaro
K
Nakayama
Hiroki
H
Otani
Kohji
K
Miyazaki
D000328:Adult; D000368:Aged; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D016022:Case-Control Studies; D003338:Corpus Luteum / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism; D010053:Ovary / Q000378:metabolism*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D042787:Receptor, TIE-2; D020133:Reverse Transcriptase Polymerase Chain Reaction
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D017931:DNA Primers; D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2