Aurora-A overexpression enhances cell-aggregation of Ha-<it>ras </it>transformants through the MEK/ERK signaling pathway
<p>Abstract</p> <p>Background</p> <p>Overexpression of Aurora-A and mutant Ras (Ras<sup>V12</sup>) together has been detected in human bladder cancer tissue. However, it is not clear whether this phenomenon is a general event or not. Although crosstalk betwe...
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| Format: | Article |
| Language: | English |
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BMC
2009-12-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/9/435 |
| _version_ | 1811296999951040512 |
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| author | Huang Chi-Ying F Lee Jenq-Chang Tseng Ya-Shih Liu Hsiao-Sheng |
| author_facet | Huang Chi-Ying F Lee Jenq-Chang Tseng Ya-Shih Liu Hsiao-Sheng |
| author_sort | Huang Chi-Ying F |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Overexpression of Aurora-A and mutant Ras (Ras<sup>V12</sup>) together has been detected in human bladder cancer tissue. However, it is not clear whether this phenomenon is a general event or not. Although crosstalk between Aurora-A and Ras signaling pathways has been reported, the role of these two genes acting together in tumorigenesis remains unclear.</p> <p>Methods</p> <p>Real-time PCR and sequence analysis were utilized to identify Ha- and Ki-<it>ras </it>mutation (Gly -> Val). Immunohistochemistry staining was used to measure the level of Aurora-A expression in bladder and colon cancer specimens. To reveal the effect of overexpression of the above two genes on cellular responses, mouse NIH3T3 fibroblast derived cell lines over-expressing either Ras<sup>V12</sup>and wild-type Aurora-A (designated WT) or Ras<sup>V12 </sup>and kinase-inactivated Aurora-A (KD) were established. MTT and focus formation assays were conducted to measure proliferation rate and focus formation capability of the cells. Small interfering RNA, pharmacological inhibitors and dominant negative genes were used to dissect the signaling pathways involved.</p> <p>Results</p> <p>Overexpression of wild-type Aurora-A and mutation of Ras<sup>V12 </sup>were detected in human bladder and colon cancer tissues. Wild-type Aurora-A induces focus formation and aggregation of the Ras<sup>V12 </sup>transformants. Aurora-A activates Ral A and the phosphorylation of AKT as well as enhances the phosphorylation of MEK, ERK of WT cells. Finally, the Ras/MEK/ERK signaling pathway is responsible for Aurora-A induced aggregation of the Ras<sup>V12 </sup>transformants.</p> <p>Conclusion</p> <p>Wild-type-Aurora-A enhances focus formation and aggregation of the Ras<sup>V12 </sup>transformants and the latter occurs through modulating the Ras/MEK/ERK signaling pathway.</p> |
| first_indexed | 2024-04-13T05:57:37Z |
| format | Article |
| id | doaj.art-33ee061c4a3e4c79bbeca116a025282f |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T05:57:37Z |
| publishDate | 2009-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-33ee061c4a3e4c79bbeca116a025282f2022-12-22T02:59:34ZengBMCBMC Cancer1471-24072009-12-019143510.1186/1471-2407-9-435Aurora-A overexpression enhances cell-aggregation of Ha-<it>ras </it>transformants through the MEK/ERK signaling pathwayHuang Chi-Ying FLee Jenq-ChangTseng Ya-ShihLiu Hsiao-Sheng<p>Abstract</p> <p>Background</p> <p>Overexpression of Aurora-A and mutant Ras (Ras<sup>V12</sup>) together has been detected in human bladder cancer tissue. However, it is not clear whether this phenomenon is a general event or not. Although crosstalk between Aurora-A and Ras signaling pathways has been reported, the role of these two genes acting together in tumorigenesis remains unclear.</p> <p>Methods</p> <p>Real-time PCR and sequence analysis were utilized to identify Ha- and Ki-<it>ras </it>mutation (Gly -> Val). Immunohistochemistry staining was used to measure the level of Aurora-A expression in bladder and colon cancer specimens. To reveal the effect of overexpression of the above two genes on cellular responses, mouse NIH3T3 fibroblast derived cell lines over-expressing either Ras<sup>V12</sup>and wild-type Aurora-A (designated WT) or Ras<sup>V12 </sup>and kinase-inactivated Aurora-A (KD) were established. MTT and focus formation assays were conducted to measure proliferation rate and focus formation capability of the cells. Small interfering RNA, pharmacological inhibitors and dominant negative genes were used to dissect the signaling pathways involved.</p> <p>Results</p> <p>Overexpression of wild-type Aurora-A and mutation of Ras<sup>V12 </sup>were detected in human bladder and colon cancer tissues. Wild-type Aurora-A induces focus formation and aggregation of the Ras<sup>V12 </sup>transformants. Aurora-A activates Ral A and the phosphorylation of AKT as well as enhances the phosphorylation of MEK, ERK of WT cells. Finally, the Ras/MEK/ERK signaling pathway is responsible for Aurora-A induced aggregation of the Ras<sup>V12 </sup>transformants.</p> <p>Conclusion</p> <p>Wild-type-Aurora-A enhances focus formation and aggregation of the Ras<sup>V12 </sup>transformants and the latter occurs through modulating the Ras/MEK/ERK signaling pathway.</p>http://www.biomedcentral.com/1471-2407/9/435 |
| spellingShingle | Huang Chi-Ying F Lee Jenq-Chang Tseng Ya-Shih Liu Hsiao-Sheng Aurora-A overexpression enhances cell-aggregation of Ha-<it>ras </it>transformants through the MEK/ERK signaling pathway BMC Cancer |
| title | Aurora-A overexpression enhances cell-aggregation of Ha-<it>ras </it>transformants through the MEK/ERK signaling pathway |
| title_full | Aurora-A overexpression enhances cell-aggregation of Ha-<it>ras </it>transformants through the MEK/ERK signaling pathway |
| title_fullStr | Aurora-A overexpression enhances cell-aggregation of Ha-<it>ras </it>transformants through the MEK/ERK signaling pathway |
| title_full_unstemmed | Aurora-A overexpression enhances cell-aggregation of Ha-<it>ras </it>transformants through the MEK/ERK signaling pathway |
| title_short | Aurora-A overexpression enhances cell-aggregation of Ha-<it>ras </it>transformants through the MEK/ERK signaling pathway |
| title_sort | aurora a overexpression enhances cell aggregation of ha it ras it transformants through the mek erk signaling pathway |
| url | http://www.biomedcentral.com/1471-2407/9/435 |
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