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Conference Paper: Inactivation of Id-1 increases the sensitivity to TGF-β1-induced growth arrest in prostate epithelial cells

TitleInactivation of Id-1 increases the sensitivity to TGF-β1-induced growth arrest in prostate epithelial cells
Authors
Issue Date2006
PublisherAmerican Association for Cancer Research.
Citation
The 97th Annual Meeting of the American Association for Cancer Research (AACR 2006), Washington, DC., 1-5 April 2006. In Cancer Research, 2006, v. 66 n. 8S, p. 405, abstract no. 1719 How to Cite?
AbstractId-1 is a member of the Id (inhibitor of differentiation or DNA binding) protein family, which belongs to the helix-loop-helix (HLH) transcription factors. A growing body of evidence indicates that Id-1 is not only essential for cell cycle progression, but it may also be involved in tumorigenesis. TGF-β1, meanwhile, plays dual roles during carcinogenesis: on one hand, it inhibits the growth of most non-malignant cells, especially those of epithelial origin; on the other hand, TGF-β1 contributes to tumor aggressiveness and cells become resistant to the anti-proliferative effects of TGF-β1 during tumorigenesis. To date, several lines of evidence have suggested that TGF-β1 may be one of the negative regulators of Id-1. In addition, down-regulation of Id-1 expression by TGF-β1 is accompanied by up-regulation of p21WAF1/Cip1 and p27KIP1, both of which are associated with TGF-β1-induced growth arrest in the prostate epithelia. Hence, we have hypothesized that the presence of Id-1 in epithelial cells might be responsible for the heightened cellular resistance to the growth inhibitory effect of TGF-β1, which in turn may promote tumorigenesis. Using an immortalized prostate epithelial cell line, NPTX, we have suppressed endogenous Id-1 levels through transfection of an antisense Id-1 construct. We have found that inactivation of Id-1 down-regulated NPTX cell proliferation, and more cells were arrested at G2/M phase of cell cycle. In addition, inactivation of Id-1 would make cells more vulnerable to TGF-β1-induced growth arrest. Furthermore, the sensitization effect to TGF-β1 was associated with up-regulation of p21WAF1/Cip1 and p27KIP1, at both mRNA and protein levels. These results have suggested that down-regulation of Id-1 levels may lead to increased sensitivity to TGF-β1, which may be mediated by up-regulation of p21WAF1/Cip1 and p27KIP1. Hence, the endogenous Id-1 levels may be important in modulating the cellular response to TGF-β1-induced growth inhibitory effect. The findings from the Id-1 knock down studies likely could contribute to the design of a therapeutic strategy in which inactivation of endogenous Id-1 might sensitize malignant cells to a host of therapeutic drugs, such as TGF-β1.
Persistent Identifierhttp://hdl.handle.net/10722/95186
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorDi, Ken_HK
dc.contributor.authorLing, MTen_HK
dc.contributor.authorTsao, GSWen_HK
dc.contributor.authorWong, YCen_HK
dc.contributor.authorWang, Xen_HK
dc.date.accessioned2010-09-25T15:54:20Z-
dc.date.available2010-09-25T15:54:20Z-
dc.date.issued2006en_HK
dc.identifier.citationThe 97th Annual Meeting of the American Association for Cancer Research (AACR 2006), Washington, DC., 1-5 April 2006. In Cancer Research, 2006, v. 66 n. 8S, p. 405, abstract no. 1719en_HK
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/95186-
dc.description.abstractId-1 is a member of the Id (inhibitor of differentiation or DNA binding) protein family, which belongs to the helix-loop-helix (HLH) transcription factors. A growing body of evidence indicates that Id-1 is not only essential for cell cycle progression, but it may also be involved in tumorigenesis. TGF-β1, meanwhile, plays dual roles during carcinogenesis: on one hand, it inhibits the growth of most non-malignant cells, especially those of epithelial origin; on the other hand, TGF-β1 contributes to tumor aggressiveness and cells become resistant to the anti-proliferative effects of TGF-β1 during tumorigenesis. To date, several lines of evidence have suggested that TGF-β1 may be one of the negative regulators of Id-1. In addition, down-regulation of Id-1 expression by TGF-β1 is accompanied by up-regulation of p21WAF1/Cip1 and p27KIP1, both of which are associated with TGF-β1-induced growth arrest in the prostate epithelia. Hence, we have hypothesized that the presence of Id-1 in epithelial cells might be responsible for the heightened cellular resistance to the growth inhibitory effect of TGF-β1, which in turn may promote tumorigenesis. Using an immortalized prostate epithelial cell line, NPTX, we have suppressed endogenous Id-1 levels through transfection of an antisense Id-1 construct. We have found that inactivation of Id-1 down-regulated NPTX cell proliferation, and more cells were arrested at G2/M phase of cell cycle. In addition, inactivation of Id-1 would make cells more vulnerable to TGF-β1-induced growth arrest. Furthermore, the sensitization effect to TGF-β1 was associated with up-regulation of p21WAF1/Cip1 and p27KIP1, at both mRNA and protein levels. These results have suggested that down-regulation of Id-1 levels may lead to increased sensitivity to TGF-β1, which may be mediated by up-regulation of p21WAF1/Cip1 and p27KIP1. Hence, the endogenous Id-1 levels may be important in modulating the cellular response to TGF-β1-induced growth inhibitory effect. The findings from the Id-1 knock down studies likely could contribute to the design of a therapeutic strategy in which inactivation of endogenous Id-1 might sensitize malignant cells to a host of therapeutic drugs, such as TGF-β1.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofCancer Researchen_HK
dc.titleInactivation of Id-1 increases the sensitivity to TGF-β1-induced growth arrest in prostate epithelial cellsen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLing, MT: patling@HKUCC.hku.hken_HK
dc.identifier.emailTsao, GSW: gswtsao@hkucc.hku.hken_HK
dc.identifier.emailWong, YC: ycwong@hkucc.hku.hken_HK
dc.identifier.authorityLing, MT=rp00449en_HK
dc.identifier.authorityTsao, GSW=rp00399en_HK
dc.identifier.authorityWong, YC=rp00316en_HK
dc.identifier.hkuros131076en_HK
dc.identifier.spage405, abstract no. 1719en_HK
dc.identifier.epage405, abstract no. 1719-

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