File Download
Supplementary

Conference Paper: Identification of microRNAs associated with tamoxifen resistance in breast cancer

TitleIdentification of microRNAs associated with tamoxifen resistance in breast cancer
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research.
Citation
The 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington D.C., 17-21 April 2010. How to Cite?
AbstractTamoxifen is the most commonly used endocrine therapy for estrogen receptor-positive breast cancer patients. As an estrogen antagonist, tamoxifen competes for binding with estrogen receptor, thereby inhibiting estrogen-dependent gene transcription and tumor growth. However, some breast tumors become estrogen-independent and ultimately develop resistance to the treatment. The mechanisms underlying this transition in the control of cell proliferation remain unclear. Recent work has shown that aberrant expression of microRNAs has been frequently detected in breast cancer and some of which are associated with breast cancer metastasis, poor prognosis, suggesting an important role of microRNAs in breast cancer development and progression. Certain microRNAs negatively regulate AIB1/ACTR, ERα, HER2 and HER3 and deregulation of these genes are well documented to modulate the resistance to tamoxifen in breast cancer. Therefore, we hypothesized that deregulated microRNAs might confer the aberrant expression of their target genes and the development of tamoxifen resistance in breast cancer. To identify microRNAs that might confer resistance to tamoxifen in breast cancer, we examined expression profiles of more than 600 microRNAs in a pair of tamoxifen-sensitive ZR75 and -resistant AK47 breast cancer cell lines using TaqMan Low Density Array (Applied Biosystems). Sixty-five microRNAs were identified substantially downmodulated in the tamoxifen-resistant cell line while 44 microRNAs were found to be upregulated. Consistent with others’ previous findings, our profiling results indicated that miR-221 and miR-222 were overexpressed in the tamoxifen-resistant breast cancer cells. Of the differentially expressed microRNAs, miR-449a and miR-449b were significantly downregulated in the resistant AK47 cells. miR-449a/b expression was also examined in 60 frozen breast tumors by TaqMan Individual MicroRNA Assay (Applied Biosystems). The expression of miR-449a/b was inversely correlated with tumor grade (miR-449a: OR=0.11, 95%CI=0.03-0.38, p<0.001; miR-449b: OR=0.23, 95%CI=0.07-0.70, p=0.008) and strongly associated with estrogen receptor status of the tumor (miR-449a: OR=5.57, 95%CI=1.67-18.55, p=0.003; miR-449b: OR=5.0, 95%CI=1.51-16.56, p=0.006). Our results suggest that miR-449a/b may influence tamoxifen sensitivity in breast cancer cells. Further functional studies are being performed to investigate the regulatory roles of the microRNAs in the development of tamoxifen resistance in breast cancer.
DescriptionPoster Session 3 - PO.CB.13.01: MicroRNA-Mediated Regulation of Cancer Biology 2: abstract no. 2040
Persistent Identifierhttp://hdl.handle.net/10722/126690

 

DC FieldValueLanguage
dc.contributor.authorLau, LYen_HK
dc.contributor.authorChan, KYKen_HK
dc.contributor.authorKhoo, USen_HK
dc.date.accessioned2010-10-31T12:42:54Z-
dc.date.available2010-10-31T12:42:54Z-
dc.date.issued2010en_HK
dc.identifier.citationThe 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington D.C., 17-21 April 2010.en_HK
dc.identifier.urihttp://hdl.handle.net/10722/126690-
dc.descriptionPoster Session 3 - PO.CB.13.01: MicroRNA-Mediated Regulation of Cancer Biology 2: abstract no. 2040-
dc.description.abstractTamoxifen is the most commonly used endocrine therapy for estrogen receptor-positive breast cancer patients. As an estrogen antagonist, tamoxifen competes for binding with estrogen receptor, thereby inhibiting estrogen-dependent gene transcription and tumor growth. However, some breast tumors become estrogen-independent and ultimately develop resistance to the treatment. The mechanisms underlying this transition in the control of cell proliferation remain unclear. Recent work has shown that aberrant expression of microRNAs has been frequently detected in breast cancer and some of which are associated with breast cancer metastasis, poor prognosis, suggesting an important role of microRNAs in breast cancer development and progression. Certain microRNAs negatively regulate AIB1/ACTR, ERα, HER2 and HER3 and deregulation of these genes are well documented to modulate the resistance to tamoxifen in breast cancer. Therefore, we hypothesized that deregulated microRNAs might confer the aberrant expression of their target genes and the development of tamoxifen resistance in breast cancer. To identify microRNAs that might confer resistance to tamoxifen in breast cancer, we examined expression profiles of more than 600 microRNAs in a pair of tamoxifen-sensitive ZR75 and -resistant AK47 breast cancer cell lines using TaqMan Low Density Array (Applied Biosystems). Sixty-five microRNAs were identified substantially downmodulated in the tamoxifen-resistant cell line while 44 microRNAs were found to be upregulated. Consistent with others’ previous findings, our profiling results indicated that miR-221 and miR-222 were overexpressed in the tamoxifen-resistant breast cancer cells. Of the differentially expressed microRNAs, miR-449a and miR-449b were significantly downregulated in the resistant AK47 cells. miR-449a/b expression was also examined in 60 frozen breast tumors by TaqMan Individual MicroRNA Assay (Applied Biosystems). The expression of miR-449a/b was inversely correlated with tumor grade (miR-449a: OR=0.11, 95%CI=0.03-0.38, p<0.001; miR-449b: OR=0.23, 95%CI=0.07-0.70, p=0.008) and strongly associated with estrogen receptor status of the tumor (miR-449a: OR=5.57, 95%CI=1.67-18.55, p=0.003; miR-449b: OR=5.0, 95%CI=1.51-16.56, p=0.006). Our results suggest that miR-449a/b may influence tamoxifen sensitivity in breast cancer cells. Further functional studies are being performed to investigate the regulatory roles of the microRNAs in the development of tamoxifen resistance in breast cancer.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofAnnual Meeting of the American Association for Cancer Research-
dc.titleIdentification of microRNAs associated with tamoxifen resistance in breast canceren_HK
dc.typeConference_Paperen_HK
dc.identifier.emailChan, KYK: ykchanc@hku.hken_HK
dc.identifier.emailKhoo, US: uskhoo@pathology.hku.hk, uskhoo@hkucc.hku.hken_HK
dc.identifier.authorityChan, KYK=rp00453en_HK
dc.identifier.authorityKhoo, US=rp00362en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros176359en_HK
dc.publisher.placeUnited States-
dc.description.otherThe 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington D.C., 17-21 April 2010.-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats