In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression.
Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM) 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3547060?pdf=render |
| _version_ | 1818011296582336512 |
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| author | Che-Ming Liu Chia-Ling Hsieh Yun-Chi He Sen-Jei Lo Ji-An Liang Teng-Fu Hsieh Sajni Josson Leland W K Chung Mien-Chie Hung Shian-Ying Sung |
| author_facet | Che-Ming Liu Chia-Ling Hsieh Yun-Chi He Sen-Jei Lo Ji-An Liang Teng-Fu Hsieh Sajni Josson Leland W K Chung Mien-Chie Hung Shian-Ying Sung |
| author_sort | Che-Ming Liu |
| collection | DOAJ |
| description | Cancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM) 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene expression by lentivirus-delivered small hairpin RNA (shRNA) significantly inhibited proliferation of human prostate cancer cell lines and blocked tumor growth in a murine model of prostate cancer bone metastasis. Cell cycle studies confirmed an increase in the G1-phase and decrease in the S-phase population of cancer cells under starvation stress conditions, which correlated with elevated intracellular superoxide levels. Microarray data showed significantly decreased levels of regenerating islet-derived family member 4 (REG4) expression in prostate cancer cells with knockdown of ADAM9 gene expression. This REG4 downregulation also resulted in induction of expression of p21(Cip1/WAF1), which negatively regulates cyclin D1 and blocks the G1/S transition. Our data reveal a novel molecular mechanism of ADAM9 in the regulation of prostate cancer cell proliferation, and suggests a combined modality of ADAM9 shRNA gene therapy and cytotoxic agents for hormone refractory and bone metastatic prostate cancer. |
| first_indexed | 2024-04-14T06:06:56Z |
| format | Article |
| id | doaj.art-c63903ff83684e208be0ea9cc9bc347e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T06:06:56Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c63903ff83684e208be0ea9cc9bc347e2022-12-22T02:08:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5379510.1371/journal.pone.0053795In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression.Che-Ming LiuChia-Ling HsiehYun-Chi HeSen-Jei LoJi-An LiangTeng-Fu HsiehSajni JossonLeland W K ChungMien-Chie HungShian-Ying SungCancer cells respond to stress by activating a variety of survival signaling pathways. A disintegrin and metalloproteinase (ADAM) 9 is upregulated during cancer progression and hormone therapy, functioning in part through an increase in reactive oxygen species. Here, we present in vitro and in vivo evidence that therapeutic targeting of ADAM9 gene expression by lentivirus-delivered small hairpin RNA (shRNA) significantly inhibited proliferation of human prostate cancer cell lines and blocked tumor growth in a murine model of prostate cancer bone metastasis. Cell cycle studies confirmed an increase in the G1-phase and decrease in the S-phase population of cancer cells under starvation stress conditions, which correlated with elevated intracellular superoxide levels. Microarray data showed significantly decreased levels of regenerating islet-derived family member 4 (REG4) expression in prostate cancer cells with knockdown of ADAM9 gene expression. This REG4 downregulation also resulted in induction of expression of p21(Cip1/WAF1), which negatively regulates cyclin D1 and blocks the G1/S transition. Our data reveal a novel molecular mechanism of ADAM9 in the regulation of prostate cancer cell proliferation, and suggests a combined modality of ADAM9 shRNA gene therapy and cytotoxic agents for hormone refractory and bone metastatic prostate cancer.http://europepmc.org/articles/PMC3547060?pdf=render |
| spellingShingle | Che-Ming Liu Chia-Ling Hsieh Yun-Chi He Sen-Jei Lo Ji-An Liang Teng-Fu Hsieh Sajni Josson Leland W K Chung Mien-Chie Hung Shian-Ying Sung In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression. PLoS ONE |
| title | In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression. |
| title_full | In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression. |
| title_fullStr | In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression. |
| title_full_unstemmed | In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression. |
| title_short | In vivo targeting of ADAM9 gene expression using lentivirus-delivered shRNA suppresses prostate cancer growth by regulating REG4 dependent cell cycle progression. |
| title_sort | in vivo targeting of adam9 gene expression using lentivirus delivered shrna suppresses prostate cancer growth by regulating reg4 dependent cell cycle progression |
| url | http://europepmc.org/articles/PMC3547060?pdf=render |
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