Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors
<p>Abstract</p> <p>Background</p> <p>Inhibitor of differentiation 2 (<it>Id2</it>) is a critical factor for cell proliferation and differentiation in normal vertebrate development. Most of the biological function of Id2 has been ascribed to its helix-loop-he...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-03-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/9/75 |
| _version_ | 1811246200896094208 |
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| author | Si Yiling Zhao Yali Wu Zhiqiang Gu Chenglei Meng Yuanguang Fu Xiaobing Han Weidong |
| author_facet | Si Yiling Zhao Yali Wu Zhiqiang Gu Chenglei Meng Yuanguang Fu Xiaobing Han Weidong |
| author_sort | Si Yiling |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Inhibitor of differentiation 2 (<it>Id2</it>) is a critical factor for cell proliferation and differentiation in normal vertebrate development. Most of the biological function of Id2 has been ascribed to its helix-loop-helix motif. Overexpression of Id2 is frequently observed in various human tumors, but its role for invasion potential in tumor cells is dispute. We aimed to reveal the role of Id2 in invasion potential in poorly invasive and estrogen receptor α (ERα)-positive MCF-7 and SKOV-3 cancer cells.</p> <p>Methods</p> <p>MCF-7 and SKOV-3 cells were stably transfected with the wild-type, degradation-resistant full-length or helix-loop-helix (HLH)-deleted Id2, respectively. Protein levels of Id2 and its mutants and E-cadherin were determined by western blot analysis and mRNA levels of Id2 and its mutants were determined by RT-PCR. The effects of Id2 and its mutants on cell proliferation were determined by [<sup>3</sup>H]-thymidine incorporation assay and the 3- [4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) dye method. The <it>in vitro </it>invasion potential of cells was evaluated by Transwell assay. Cell motility was assessed by scratch wound assay. The promoter activity of <it>E-cadherin </it>was determined by cotransfection and luciferase assays.</p> <p>Results</p> <p>Ectopic transfection of the wild-type Id2 markedly increased the protein and mRNA expression of <it>Id2 </it>in MCF-7 and SKOV-3 cells; the protein level but not mRNA level was further increased by transfection with the degradation-resistant Id2 form. The ectopic expression of Id2 or its mutants did not alter proliferation of either MCF-7 or SKOV-3 cells. Transfection of the wild-type Id2 significantly induced the invasion potential and migratory capacity of cells, which was further augmented by transfection with the degradation-resistant full-length or HLH-deleted Id2. E-cadherin protein expression and transactivation of the proximal E-cadherin promoter were markedly suppressed by the degradation-resistant full-length or HLH-deleted Id2 but not wild-type Id2. Ectopic expression of E-cadherin in MCF-7 and SKOV-3 cells only partially blunted the invasion potential induced by the degradation-resistant HLH-deleted Id2.</p> <p>Conclusion</p> <p>Overexpression of Id2 in ERα-positive epithelial tumor cells indeed increases the cells' invasive potential through a novel mechanism independent of dimerization to basic helix-loop-helix factors. E-cadherin contributes only in part to Id2-induced cell invasion when Id2 is accumulated to a higher level in some specific cell types.</p> |
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| id | doaj.art-e62df3c6fb2a497485616c94f5759a7a |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
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| publishDate | 2009-03-01 |
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| spelling | doaj.art-e62df3c6fb2a497485616c94f5759a7a2022-12-22T03:28:31ZengBMCBMC Cancer1471-24072009-03-01917510.1186/1471-2407-9-75Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factorsSi YilingZhao YaliWu ZhiqiangGu ChengleiMeng YuanguangFu XiaobingHan Weidong<p>Abstract</p> <p>Background</p> <p>Inhibitor of differentiation 2 (<it>Id2</it>) is a critical factor for cell proliferation and differentiation in normal vertebrate development. Most of the biological function of Id2 has been ascribed to its helix-loop-helix motif. Overexpression of Id2 is frequently observed in various human tumors, but its role for invasion potential in tumor cells is dispute. We aimed to reveal the role of Id2 in invasion potential in poorly invasive and estrogen receptor α (ERα)-positive MCF-7 and SKOV-3 cancer cells.</p> <p>Methods</p> <p>MCF-7 and SKOV-3 cells were stably transfected with the wild-type, degradation-resistant full-length or helix-loop-helix (HLH)-deleted Id2, respectively. Protein levels of Id2 and its mutants and E-cadherin were determined by western blot analysis and mRNA levels of Id2 and its mutants were determined by RT-PCR. The effects of Id2 and its mutants on cell proliferation were determined by [<sup>3</sup>H]-thymidine incorporation assay and the 3- [4, 5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) dye method. The <it>in vitro </it>invasion potential of cells was evaluated by Transwell assay. Cell motility was assessed by scratch wound assay. The promoter activity of <it>E-cadherin </it>was determined by cotransfection and luciferase assays.</p> <p>Results</p> <p>Ectopic transfection of the wild-type Id2 markedly increased the protein and mRNA expression of <it>Id2 </it>in MCF-7 and SKOV-3 cells; the protein level but not mRNA level was further increased by transfection with the degradation-resistant Id2 form. The ectopic expression of Id2 or its mutants did not alter proliferation of either MCF-7 or SKOV-3 cells. Transfection of the wild-type Id2 significantly induced the invasion potential and migratory capacity of cells, which was further augmented by transfection with the degradation-resistant full-length or HLH-deleted Id2. E-cadherin protein expression and transactivation of the proximal E-cadherin promoter were markedly suppressed by the degradation-resistant full-length or HLH-deleted Id2 but not wild-type Id2. Ectopic expression of E-cadherin in MCF-7 and SKOV-3 cells only partially blunted the invasion potential induced by the degradation-resistant HLH-deleted Id2.</p> <p>Conclusion</p> <p>Overexpression of Id2 in ERα-positive epithelial tumor cells indeed increases the cells' invasive potential through a novel mechanism independent of dimerization to basic helix-loop-helix factors. E-cadherin contributes only in part to Id2-induced cell invasion when Id2 is accumulated to a higher level in some specific cell types.</p>http://www.biomedcentral.com/1471-2407/9/75 |
| spellingShingle | Si Yiling Zhao Yali Wu Zhiqiang Gu Chenglei Meng Yuanguang Fu Xiaobing Han Weidong Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors BMC Cancer |
| title | Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors |
| title_full | Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors |
| title_fullStr | Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors |
| title_full_unstemmed | Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors |
| title_short | Id2 promotes the invasive growth of MCF-7 and SKOV-3 cells by a novel mechanism independent of dimerization to basic helix-loop-helix factors |
| title_sort | id2 promotes the invasive growth of mcf 7 and skov 3 cells by a novel mechanism independent of dimerization to basic helix loop helix factors |
| url | http://www.biomedcentral.com/1471-2407/9/75 |
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