Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1
<p>Abstract</p> <p>Background</p> <p>In our previous study, we detected decreased expression of phospho-Smad1/5/8 and its upstream signaling molecule, bone morphogenetic protein receptor IB subunit (BMPR-IB), in certain glioblastoma tissues, unlike normal brain tissues....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-05-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://www.jeccr.com/content/31/1/52 |
| _version_ | 1818039522633449472 |
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| author | Liu Shuang Yin Feng Fan Wenhong Wang Shuwei Guo Xin-ru Zhang Jian-ning Tian Zeng-min Fan Ming |
| author_facet | Liu Shuang Yin Feng Fan Wenhong Wang Shuwei Guo Xin-ru Zhang Jian-ning Tian Zeng-min Fan Ming |
| author_sort | Liu Shuang |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>In our previous study, we detected decreased expression of phospho-Smad1/5/8 and its upstream signaling molecule, bone morphogenetic protein receptor IB subunit (BMPR-IB), in certain glioblastoma tissues, unlike normal brain tissues. In order to clarify the functional roles and mechanism of BMPR-IB in the development of glioblastoma, we studied the effects of BMPR-IB overexpression on glioblastoma cell lines in vitro and in vivo.</p> <p>Methods</p> <p>We selected glioblastoma cell lines U251, U87, SF763, which have different expression of BMPR-IB to be the research subjects. Colony formation analysis and FACS were used to detect the effects of BMPR-IB on the growth and proliferation of glioblastoma cells in vivo. Immunofluresence was used to detect the differentiation changes after BMPR-IB overexpression or knocking-down. Then we used subcutaneous and intracranial tumor models to study the effect of BMPR-IB on the growth and differentiation of glioblastoma cells in vivo. The genetic alterations involved in this process were examined by real-time PCR and western blot analysis.ed.</p> <p>Results and conclusion</p> <p>Forced BMPR-IB expression in malignant human glioma cells, which exhibit lower expression of BMPR-IB, induced the phosphorylation and nuclear localization of smad1/5/8 and arrested the cell cycle in G1. Additionally, BMPR-IB overexpression could suppress anchorage-independent growth and promote differentiation of theses glioblastoma cells. Furthermore, overexpression of BMPR-IB inhibited the growth of subcutaneous and intracranial tumor xenografts and prolonged the survival of mice injected intracranially with BMPR-IB-overexpressing glioblastoma cells. Conversely, inhibition of BMPR-IB caused SF763 malignant glioma cells, a line known to exhibit high BMPR-IB expression that does not form tumors when used for xenografts, to show increased growth and regain tumorigenicity in a nude mouse model system, ultimately shortening the survival of these mice. We also observed significant accumulation of p21 and p27kip1 proteins in response to BMPR-IB overexpression. Our study suggests that overexpression of BMPR-IB may arrest and induce the differentiation of glioblastoma cells due to upregulation of p21 and p27kip1 in vitro and that in vivo and decreased expression of BMPR-IB in human glioblastoma cells contributes to glioma tumorigenicity. BMPR-IB could represent a new potential therapeutic target for malignant human gliomas.</p> |
| first_indexed | 2024-12-10T07:59:58Z |
| format | Article |
| id | doaj.art-c1b0d083681e4e01b9937baa302410c1 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-10T07:59:58Z |
| publishDate | 2012-05-01 |
| publisher | BMC |
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| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-c1b0d083681e4e01b9937baa302410c12022-12-22T01:56:48ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662012-05-013115210.1186/1756-9966-31-52Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1Liu ShuangYin FengFan WenhongWang ShuweiGuo Xin-ruZhang Jian-ningTian Zeng-minFan Ming<p>Abstract</p> <p>Background</p> <p>In our previous study, we detected decreased expression of phospho-Smad1/5/8 and its upstream signaling molecule, bone morphogenetic protein receptor IB subunit (BMPR-IB), in certain glioblastoma tissues, unlike normal brain tissues. In order to clarify the functional roles and mechanism of BMPR-IB in the development of glioblastoma, we studied the effects of BMPR-IB overexpression on glioblastoma cell lines in vitro and in vivo.</p> <p>Methods</p> <p>We selected glioblastoma cell lines U251, U87, SF763, which have different expression of BMPR-IB to be the research subjects. Colony formation analysis and FACS were used to detect the effects of BMPR-IB on the growth and proliferation of glioblastoma cells in vivo. Immunofluresence was used to detect the differentiation changes after BMPR-IB overexpression or knocking-down. Then we used subcutaneous and intracranial tumor models to study the effect of BMPR-IB on the growth and differentiation of glioblastoma cells in vivo. The genetic alterations involved in this process were examined by real-time PCR and western blot analysis.ed.</p> <p>Results and conclusion</p> <p>Forced BMPR-IB expression in malignant human glioma cells, which exhibit lower expression of BMPR-IB, induced the phosphorylation and nuclear localization of smad1/5/8 and arrested the cell cycle in G1. Additionally, BMPR-IB overexpression could suppress anchorage-independent growth and promote differentiation of theses glioblastoma cells. Furthermore, overexpression of BMPR-IB inhibited the growth of subcutaneous and intracranial tumor xenografts and prolonged the survival of mice injected intracranially with BMPR-IB-overexpressing glioblastoma cells. Conversely, inhibition of BMPR-IB caused SF763 malignant glioma cells, a line known to exhibit high BMPR-IB expression that does not form tumors when used for xenografts, to show increased growth and regain tumorigenicity in a nude mouse model system, ultimately shortening the survival of these mice. We also observed significant accumulation of p21 and p27kip1 proteins in response to BMPR-IB overexpression. Our study suggests that overexpression of BMPR-IB may arrest and induce the differentiation of glioblastoma cells due to upregulation of p21 and p27kip1 in vitro and that in vivo and decreased expression of BMPR-IB in human glioblastoma cells contributes to glioma tumorigenicity. BMPR-IB could represent a new potential therapeutic target for malignant human gliomas.</p>http://www.jeccr.com/content/31/1/521. BMPR-IB2. Glioblastoma3. Growth inhibition4. Differentiation |
| spellingShingle | Liu Shuang Yin Feng Fan Wenhong Wang Shuwei Guo Xin-ru Zhang Jian-ning Tian Zeng-min Fan Ming Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1 Journal of Experimental & Clinical Cancer Research 1. BMPR-IB 2. Glioblastoma 3. Growth inhibition 4. Differentiation |
| title | Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1 |
| title_full | Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1 |
| title_fullStr | Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1 |
| title_full_unstemmed | Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1 |
| title_short | Over-expression of BMPR-IB reduces the malignancy of glioblastoma cells by upregulation of p21 and p27Kip1 |
| title_sort | over expression of bmpr ib reduces the malignancy of glioblastoma cells by upregulation of p21 and p27kip1 |
| topic | 1. BMPR-IB 2. Glioblastoma 3. Growth inhibition 4. Differentiation |
| url | http://www.jeccr.com/content/31/1/52 |
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