Abstract:
:Breast cancer is the most common carcinoma that metastasizes to bone. Tumor-produced parathyroid hormone-related protein (PTHrP), a known stimulator of osteoclastic bone resorption, is a major mediator of the osteolytic process in breast cancer. We have previously shown that PTHrP increases breast cancer cell proliferation, survival, migration, and pro-invasive integrin alpha6beta4 expression. To determine the role of integrin alpha6beta4 in these PTHrP-mediated effects, we utilized two strategies to modulate expression of the alpha6 and beta4 subunits in parental and PTHrP-overexpressing MDA-MB-231 and MCF-7 cells: overexpression of alpha6beta4 by transfection with constructs encoding the alpha6 and beta4 subunits, and suppression of endogenous alpha6beta4 expression by transfection with siRNAs targeting these subunits. We now show that the effects of PTHrP are mediated via upregulation of integrin alpha6beta4 expression. We also show that integrin alpha6beta4 expression is modulated at the mRNA level, indicating a transcriptional and/or post-transcriptional mechanism of action for PTHrP. PTHrP expression also increased the levels of phosphorylated Akt, with a consequent increase in the levels of phosphorylated (inactive) glycogen synthase kinase-3 (GSK-3). The role of PTHrP in breast cancer growth and metastasis may thus be mediated via upregulation of integrin alpha6beta4 expression and Akt activation, with consequent inactivation of GSK-3.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Shen X,Falzon Mdoi
10.1016/j.yexcr.2006.08.011subject
Has Abstractpub_date
2006-11-15 00:00:00pages
3822-34issue
19eissn
0014-4827issn
1090-2422pii
S0014-4827(06)00331-4journal_volume
312pub_type
杂志文章abstract::Bradykinin stimulates [3H]thymidine incorporation and DNA synthesis in resting, serum-deprived NIL8 hamster cells. The ED50 for this stimulation is 4.52 +/- 2.91 nM. Other kinin peptides including lys-bradykinin (kallidin) and met-lys-bradykinin also stimulate [3H]thymidine incorporation in the NIL8 cells, whereas des...
journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1006/excr.1998.4372
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journal_title:Experimental cell research
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Experimental cell research
pub_type: 杂志文章
doi:10.1016/j.yexcr.2009.08.020
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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pub_type: 杂志文章
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journal_title:Experimental cell research
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