A Mouse Fibroblast Cell Model to Study Human Papillomavirus-Associated Tumorigenesis

Angiogenesis Modulators Expression in Culture Cell Lines Positives for HPV-16 Oncoproteins

“…In cervical cancer some authors have described an increase on VEGF expression associated to the expression of viral oncoproteins E6 and E7 (12,13). We have also observed a significant and differential increment on VEGF transcription in cells expressing the viral oncoproteins.…”

“…E6 and E7 are known to induce the expression of or to transactivate some transcriptional and growth factors, e.g., c-fos, c-myc, c-Jun, TGF␤ (Transforming Growth Factor ␤) and VEGF (Vascular Endothelial Growth Factor), and these activities have been also correlated to the oncogenic potential of both oncoproteins (8,9,10,11). More recently it has been demonstrated that the expression of E6 and E7 in squamous epithelial cells from the K14HPV16 transgenic mouse is related to the early onset of the angiogenic response and the induction of VEGF expression in tumoral tissues (12,13). In human cervical cancer, angiogenesis appears since the premalignant stages and it is an important element to characterize disease evolution (14).…”

Thermosetting Gel for the Delivery of 5-Aminolevulinic Acid Esters to the Cervix

“…However, this model should be still valid for the relative assessment of porphyrin induction induced by different formulations, and can be considered as a simple intermediate between in vitro methods and more sophisticated experiments such as xenograft animal models, which cannot simulate the intended topical administration. [44][45][46][47] Interestingly, the porphyrin build-up in vivo seems to be better related to in vitro release-time profiles into octanol than into PBS. While there is a significant difference between the total release of HAL from the HEC-containing hydrogel and the other formulations after 7.5 h, at this time point, no difference can be seen between the HAL-loaded P407 thermosetting gel and the cold cream formulation.…”

Aberrant expression of VEGF-C is related to grade of cervical intraepithelial neoplasia (CIN) and high risk HPV, but does not predict virus clearance after treatment of CIN or prognosis of cervical cancer

“…Angiogenesis is stimulated by members of the vascular endothelial growth factor (VEGF) family, which are also upregulated by the HR-HPV E6 oncoprotein. [10][11][12][13][14] ''Recently, angiogenesis has been shown to play an important role in the development of an invasive phenotype in cancer precursors (cervical intraepithelial neoplasia)'' VEGF is the primary member of a family of growth factors, which together with its homologues conveys regulatory signals via KDF/Flk-1, Flt-1, and Flt-4 receptors. 14 VEGF is one of the most potent known angiogenic factors.…”

“…The VEGF gene is located on chromosome region 6p12, and is amplified in most human malignancies. [10][11][12][13][14][15] The well established upregulators of VEGF in malignant tumours include hypoxia, mutations of ras, receptor tyrosine kinases (such as, epidermal growth factor receptor, erbB-2/Her-2), non-receptor kinases (such as src), several protooncogenes encoding transcription factors (such as, myc, c-fos, c-jun), 11 14 and members of the cyclooxygenase (COX) family (for example, COX-1 and COX2). 14 15 Another important step in VEGF upregulation was shown to be the loss of wild-type p53 function, 16 raising the possibility that HPV16 E6 was also actively involved.…”