2008年9月
Ras modifies proliferation and invasiveness of cells expressing human papillomavirus oncoproteins
JOURNAL OF VIROLOGY
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- 巻
- 82
- 号
- 17
- 開始ページ
- 8820
- 終了ページ
- 8827
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1128/JVI.02363-07
- 出版者・発行元
- AMER SOC MICROBIOLOGY
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.
- リンク情報
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- DOI
- https://doi.org/10.1128/JVI.02363-07
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902267500752449
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/18579583
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000258603600053&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1128/JVI.02363-07
- ISSN : 0022-538X
- J-Global ID : 200902267500752449
- PubMed ID : 18579583
- Web of Science ID : WOS:000258603600053