Id-1 promotes cell proliferation through the activation of EGFR, NF-κB p50 homodimer and Bcl-3 in MCF-7 breast cancer cell line

Pao Yue-kong Library Electronic Theses Database

Id-1 promotes cell proliferation through the activation of EGFR, NF-κB p50 homodimer and Bcl-3 in MCF-7 breast cancer cell line

 

Author: Ko, Wai Ting
Title: Id-1 promotes cell proliferation through the activation of EGFR, NF-κB p50 homodimer and Bcl-3 in MCF-7 breast cancer cell line
Degree: M.Phil.
Year: 2010
Subject: Breast -- Cancer -- Hormone therapy.
Breast -- Cancer -- Treatment.
Hong Kong Polytechnic University -- Dissertations
Department: Dept. of Health Technology and Informatics
Pages: xvii, 139 leaves : ill. (some col.) ; 30 cm.
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b2530043
URI: http://theses.lib.polyu.edu.hk/handle/200/6688
Abstract: Progression of breast cancer from hormone-dependent to hormone-independent causes a major problem in breast cancer therapy. The possible involvement of inhibitor of differentiation type 1 (Id-1) in this progression was suggested by the findings in our group that expression of Id-1 was higher in patients with a lower percentage of estrogen receptors (ER). Therefore, in this study, we over-expressed Id-1 in the hormone-dependent breast cancer cell line, MCF-7, to examine whether Id-1 confers growth advantage to these cells in the absence of estrogen. Our results showed that cell growth was increased in the Id-1 transfectants compared with the mock-transfected clone control over a 120 hour period. Cell growth of the transfectant was similar to the mock-transfected control after transient transfection of the Id-1 antisense oligonucleotide. Moreover, elevated levels of epidermal growth factor receptor (EGFR) which is associated with hormone-independent breast cancer, were found in Id-1 transfectants using Western blot and reverse-transcription (RT) - PCR analyses. The level of EGFR expression was decreased after transient transfection of Id-1 antisense oligonucleotide compared with the same Id-1 transfectant without Id-1 antisense oligonucleotide. The involvement of nuclear factor-kappa B (NF-κB) pathway which is one of the downstream pathways of EGFR, suggested to be activated in ER negative breast cells, was investigated. After applying an inhibitor of NF-κB, parthenolide, cell growth and cells in the S phases of the cell cycle were significantly decreased by more than 50%. Results also showed that the percentage inhibitions were positively associated with the expression levels of Id-1, implying that Id-1 may be able to activate the NF-κB pathway. Interestingly, elevated expression of nuclear fragment p50 and Bcl-3, but not p65, were observed with increased level of Id-1 using Western blotting. By contrast, the expression of IκB-α, the corresponding inhibitor of the complex of NF-κB p50/p65 heterodimers, was not correlated with the expression of Id-1. Moreover, results of electrophoretic mobility shift assay (EMSA) showed that levels of NF-κB p50 were significantly increased in Id-1 transfectants and positively associated with levels of Id-1. Our results suggest that Id-1 may be able to modulate cell growth in the absence of estrogen, possibly through the activation of EGFR signaling pathways and through the activation of NF-κB p50/p50 homodimer and Bcl-3 but not NF-κB p50/p65 heterodimer. Although further study is needed, Id-1 may serve as a biomarker in the progression of breast cancer from hormone-dependent to hormone-independent. Inactivation of Id-1 may be a potential therapeutic target for breast cancer patients who have developed resistance to hormonal therapy.

Files in this item

Files Size Format
b2530043x.pdf 1.744Mb PDF
Copyright Undertaking
As a bona fide Library user, I declare that:
  1. I will abide by the rules and legal ordinances governing copyright regarding the use of the Database.
  2. I will use the Database for the purpose of my research or private study only and not for circulation or further reproduction or any other purpose.
  3. I agree to indemnify and hold the University harmless from and against any loss, damage, cost, liability or expenses arising from copyright infringement or unauthorized usage.
By downloading any item(s) listed above, you acknowledge that you have read and understood the copyright undertaking as stated above, and agree to be bound by all of its terms.

     

Quick Search

Browse

More Information