Abstract
Objective: To investigate the mRNA expression of PTEN and vascular endothelial growth factor (VEGF) genes in ovarian cancer. Methods: We examined mRNA expression of PTEN and VEGF165 in normal ovary (n=5), ovarian cyst (n=5), ovarian borderline tumor (n=9), epithelial ovarian cancer (n=60) and ovarian cancer cell line (CAOV-3) by RT-PCR. Their expressions were compared with clinicopathological features of ovarian cancer. The relationship between their expressions was concerned in all ovarian samples as well. Results: mRNA expression level of PTEN gene was significantly lower in ovarian borderline tumor or ovarian cancer than that in normal ovary or ovarian cyst(P<0.05). It was negatively correlated with clinicopathological staging(P<0.05), whereas positively with histological differentiation (P<0.05). mRNA expression level of PTEN gene was significantly lower in ovarian endometrioid cancer than ovarian serous or mucinous cancer(P<0.05). mRNA expression level of VEGF165 gene was significantly higher in ovarian cancer than that in normal ovary or ovarian cyst(P<0.05). It was positively correlated with clinicopathological staging(P<0.05), whereas negatively with histological differentiation (P<0.05). mRNA expression level of VEGF165 gene was significantly higher in ovarian serous cancer than in other ovarian epithelial cancers (P<0.05). mRNA expression of VEGF165 gene was inversely correlated with mRNA expression level of PTEN gene. Conclusion: Down-regulated expression of PTEN and up-regulated expression of VEGF were considered as two important events in tumorigenesis of ovarian cancer and could be used as molecular markers to indicate the pathobiological behaviors of ovarian cancer. Decreased PTEN expression and increased VEGF expression were closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid and serous cancer respectively. Reduced expression of PTEN gene might be involved in carcinogenesis and progression of ovarian cancer by up-regulating the VEGF expression to enhance angiogenesis.
Similar content being viewed by others
References
Steck PA, Pershouse MA, Jasser SA, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers[J]. Nat Genet 1997; 15: 356.
Gu J, Tamura M, Yamada KM. Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathways[J]. J Cell Biol 1998; 143:1375.
Tamura M, Gu J, Takino T, et al. Tumor suppressor PTEN inhibition of cell invasion, migration and growth: differential involvement of focal adhesion kinase and p130Cas[J]. Cancer Res 1999; 59: 442.
Jones G, Machado J Jr, Tolnay M, et al. PTEN-independent induction of caspase-mediated cell death and reduced invasion by the focal adhesion targeting domain (FAT) in human astrocytic brain tumors which highly express focal adhesion kinase (FAK)[J]. Cancer Res 2001; 61:5688.
Gottschalk AR, Basila D, Wong M, et al. p27Kip1 is required for PTEN-induced G1 growth arrest[J]. Cancer Res 2001;61:2105.
Hopkin. K. A surprising function for the PTEN tumor suppressor[J]. Science 1998; 282:1027.
Cantley LC, Neel BG. New insight into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway[J]. Proc Natl Acad Sci USA 1999; 96:4240.
Huang J, Kontos CD. PTEN modulates vascular endothelial growth factor-Mediated signaling and angiogenic effects[J]. J Biol Chem 2002; 277:10760.
Byzova TV, Goldman CK, Pampori N, et al. A mechanism for modulation of cellular responses to VEGF: activation of the integrins[J]. Mol Cell 2000; 6:851.
Jiang BH, Zheng JZ, Aoki M, et al. Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells[J]. Proc Natl Acad Sci USA 2000;97:1749.
Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability and angiogenesis[J]. Am J Pathol 1995; 146:1029.
Piccinno R, Puopolo M, Rigault De La Longrais IA, et al. Growth factors in epithelial ovarian cancer[J]. Minerva Ginecol 2002; 54:33.
Bamberger ES, Perrett CW. Angiogenesis in epithelian ovarian cancer[J]. Mol Pathol 2002; 55:348.
Witte L, Hicklin DJ, Zhu Z, et al. Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy[J]. Cancer Metastasis Rev 1998; 17:155.
Barnes MN, Grizzle WE, Grubbs CJ, et al. Paradigms for primary prevention of ovarian carcinoma[J]. CA Cancer J Clin 2002; 52:216.
Waite KA, Eng C. Protean PTEN: form and function[J]. Am J Hum Genet 2002; 70:829.
Kondo K, Yao M, Kobayashi K, et al. PTEN/MMAC1/TEP1 mutations in human primary renal-cell carcinomas and renal carcinoma cell lines[J]. Int J Cancer 2001; 91:219.
Salvesen HB, MacDonald N, Ryan A, et al. PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma[J], Int J Cancer 2001; 91:22.
Geva E, Jaffe RB. Role of vascular endothelial growth factor in ovarian physiology and pathology [J]. Fertil Steril 2000; 74:429.
Sun LX, Wu Y, Han HQ, et al. Serum level and expression of vascular epithelial growth factor in ovarian epithelial carcinoma(in Chinese)[J]. Ai Zheng 2003; 22:58.
Kurose K, Zhou XP, Araki T, et al. Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas[J]. Am J Pathol 2001; 158: 2097.
Pore N, Liu S, Haas-Kogan DA, et al. PTEN mutation and epidermal growth factor receptor activation regulate vascular endothelial growth factor (VEGF) mRNA expression in human glioblastoma cells by transactivating the proximal VEGF promoter[J]. Cancer Res 2003;63:236.
Gomez-Manzano C, Fueyo J, Jiang H, et al. Mechanisms underlying PTEN regulation of vascular endothelial growth factor and angiogenesis[J]. Ann Neurol 2003; 53:109.
Author information
Authors and Affiliations
Corresponding author
Additional information
Foundation item: This work was supported by a grant from the National Natural Science Foundation of China (No. 39370772)
Biography: Chen Ying(1968-), female, candidate for doctor of medicine, associate professor, China Medical University, Shenyang Hospital of Obstetrics and Gynecology, majors in Gynecology.
Rights and permissions
About this article
Cite this article
Chen, Y., Zhao, Yj., Zheng, Hc. et al. mRNA expression of PTEN and VEGF genes in epithelial ovarian cancer. Chin J Cancer Res 15, 252–256 (2003). https://doi.org/10.1007/BF02974887
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02974887