Vascular endothelial growth factor splice variants and their prognostic value in breast and ovarian cancer.
OBJECTIVE
Vascular endothelial growth factor (VEGF) is a promotor for tumor angiogenesis, and is known to be elevated in breast and ovarian cancers. Through alternative splicing six VEGF isoforms were identified. We studied VEGF isoform expression in breast and ovarian cancer cell lines, as well as in breast carcinomas and ovarian tumors, and correlated the expression pattern with the in vitro invasiveness of the breast carcinoma cell lines and the clinicopathologic characteristics of the tumors.


METHODS
Reverse transcription-PCR and automated laser fluorescence fragment analysis were used to determine the expression of each splice variant. This method allowed the detection of all of the splice variants simultaneously, especially VEGF145 for the first time in tumor tissue.


RESULTS
VEGF121 and VEGF165 were the most dominantly expressed variants in all of the tumor samples and cell lines investigated. VEGF145 was very weakly or not expressed in breast and ovarian cancers. Statistical analysis showed no correlation between VEGF splice variant expression in the tumors and histological type, differentiation grade, tumor size, Fédération Internationale des Gynaecologistes et Obstetristes, and nodal status from cancer patients. There was also no correlation between the invasive capacity of breast cell lines and VEGF isoform expression.


CONCLUSIONS
Even though expression levels of VEGF have been shown to be important for tumor invasion and progression, the present data indicate no relation of VEGF isoform pattern with invasion and progression.
Division of Gynecology, Molecular Oncology Group, Department of Obstetrics and Gynecology, University of Vienna, A-1090 Vienna, Austria.
Margit
M
Stimpfl
Dan
D
Tong
Barbara
B
Fasching
Eva
E
Schuster
Andreas
A
Obermair
Sepp
S
Leodolter
Robert
R
Zeillinger
D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017931:DNA Primers; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors