Transcriptional deregulation of VEGF, FGF2, TGF-beta1, 2, 3 and cognate receptors in breast tumorigenesis

Autor: Demetrios A. Spandidos, George Sourvinos, Filippos Porichis, Stamatis Vassilaros, Giannoula Soufla
Rok vydání: 2004
Předmět:
Adult
Vascular Endothelial Growth Factor A
Cancer Research
medicine.medical_specialty
Transcription
Genetic
Angiogenesis
medicine.medical_treatment
Blotting
Western
Breast Neoplasms
Biology
medicine.disease_cause
Transforming Growth Factor beta1
chemistry.chemical_compound
Transforming Growth Factor beta2
Breast cancer
Transforming Growth Factor beta3
Western blot
Transforming Growth Factor beta
Internal medicine
medicine
Humans
Neoplasm Invasiveness
RNA
Messenger
RNA
Neoplasm
Aged
medicine.diagnostic_test
Reverse Transcriptase Polymerase Chain Reaction
Growth factor
Carcinoma
Ductal
Breast
Middle Aged
medicine.disease
Blot
Vascular endothelial growth factor
Gene Expression Regulation
Neoplastic
Carcinoma
Lobular
Endocrinology
Oncology
chemistry
Cancer research
Female
Fibroblast Growth Factor 2
Carcinogenesis
Receptors
Transforming Growth Factor beta
Transforming growth factor
Zdroj: Cancer letters. 235(1)
ISSN: 0304-3835
Popis: Angiogenesis is an important event during the neoplastic process and is induced by the secretion of numerous growth factors from endothelial cells. Vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (FGF2), and transforming growth factor-beta1, beta2, beta3 (TGF-beta1, 2, 3) and cognate receptors (TGF-betaRI, II, III) mRNA expression pattern was evaluated by RT-PCR in 25 breast cancer tissue samples and adjacent normal tissues, and correlated to clinicopathological features. Western blot analysis was performed to evaluate VEGF and TGF-beta1 protein levels. TGF-beta1 and TGF-beta3 mRNA levels were significantly different in breast cancer specimens of differing histology (ductal, lobular, other) (P=0.020 and P=0.043). No statistically significant difference was observed at the mRNA level of VEGF between normal and tumor tissues while elevated VEGF protein levels in tumors were associated with patients' menopausal status. A strong hormonal influence of ER and PR on TGF-beta mRNA expression was established. FGF2 transcript levels were substantially decreased in cancer compared to adjacent normal specimens (P=0.031). A disruption of mRNA co-expression patterns was observed in malignant breast tissues compared to controls. Western blot analysis revealed differences between VEGF and TGFbeta1 mRNA and their corresponding protein levels. A substantial negative correlation of TGF-beta1 protein and TGF-beta1 mRNA levels (P=0.016) was demonstrated by breast tissue-pair analysis. Summarizing, our findings suggest that transcript levels of the examined markers in breast cancer are associated with menopausal and hormonal status, while their co-expression pattern is altered in malignant tissues compared to controls. In addition the difference between VEGF and TGF-beta1 mRNA and protein levels observed, indicates that post-transcriptional mechanisms may regulate expression of these molecules in breast cancer.
Databáze: OpenAIRE
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