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Ras Modifies Proliferation and Invasiveness of Cells Expressing Human Papillomavirus Oncoproteins▿
- Publication Year :
- 2008
- Publisher :
- American Society for Microbiology (ASM), 2008.
-
Abstract
- Infection by human papillomavirus (HPV) is a major risk factor for human cervical carcinoma. However, the HPV infection alone is not sufficient for cancer formation. Cervical carcinogenesis is considered a multistep process accompanied by genetic alterations of the cell. Ras is activated in approximately 20% of human cancers, and it is related to the metastatic conversion of tumor cells. We investigated how Ras activation was involved in the malignant conversion of HPV-infected lesions. The active form of H-ras was introduced into human primary keratinocytes expressing the HPV type 18 (HPV18) oncoproteins E6 and/or E7. We analyzed the keratinocytes’ growth potentials and found that the activation of the Ras pathway induced senescence-like growth arrest. Senescence could be eliminated by high-risk E7 expression, suggesting that the pRb pathway was important for Ras-induced senescence. Then we analyzed the effect of Ras activation on epidermis development by using an organotypic “raft” culture and found that the E7 and H-ras coexpressions conferred invasive potential on the epidermis. This invasiveness resulted from the upregulation of MT1-MMP and MMP9 by H-ras and E7, respectively, in which the activation of the MEK/extracellular signal-regulated kinase pathway was involved. These results indicated that the activation of Ras or the related signal pathways promoted the malignant conversion of HPV-infected cells.
- Subjects :
- Keratinocytes
Male
Immunology
Genetic Vectors
Cell Culture Techniques
Uterine Cervical Neoplasms
Biology
Kidney
Microbiology
Retinoblastoma Protein
Transformation and Oncogenesis
Culture Media, Serum-Free
Cell Line
Organ Culture Techniques
Virology
Anti-apoptotic Ras signalling cascade
medicine
Humans
Papillomaviridae
Cells, Cultured
Cellular Senescence
Cell Line, Transformed
Epidermis (botany)
Human papillomavirus 18
Cell growth
Malignant Conversion
HPV infection
Retinoblastoma protein
Oncogene Proteins, Viral
medicine.disease
Molecular biology
Immunohistochemistry
Cell Transformation, Neoplastic
Retroviridae
Cell culture
Insect Science
Mutation
Cancer research
biology.protein
ras Proteins
Female
Cell aging
HeLa Cells
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....f5eaacf79131b5237bc8c19fc66f6a32