Abstract:
:Oxaliplatin-based chemotherapy is the mainstay for the treatment of advanced colorectal cancer. Copper transporter proteins have been implicated in the transport of platinum-based anticancer drugs, but their expression in human colorectal cancer cell lines and roles in controlling their sensitivity to oxaliplatin are not well studied or understood. The endogenous and modified expression of copper uptake transporter 1 (hCTR1) was studied in a panel of human colorectal cancer cell lines (DLD-1, SW620, HCT-15 and COLO205) with ~20-fold variation in oxaliplatin sensitivity. hCTR1 protein was expressed more abundantly than ATP7A and ATP7B proteins, but with broadly similar levels and patterns of expression across four colorectal cancer cell lines. In a colorectal cancer cell-line background (DLD-1), stable transfection of the hCtr1 gene enhanced hCTR1 protein expression and increased the sensitivity of the cells to the cytotoxicity of copper and oxaliplatin. Treatment with copper chelators (ammonium tetrathiomolybdate, bathocuproinedisulfonic acid and D-penicillamine) increased expression of hCTR1 protein in DLD-1 and SW620 cells, and potentiated the cytotoxicity of oxaliplatin in DLD-1 but not SW620 cells. Treatment with copper chloride altered neither the expression of copper transporters nor cytotoxicity of oxaliplatin in colorectal cancer lines. In conclusion, human colorectal cancer cell lines consistently express hCTR1 protein despite their variable sensitivity to oxaliplatin. Genetic or pharmacological modification of hCTR1 protein expression may potentiate oxaliplatin sensitivity in some but not all colorectal cancer cell lines.
journal_name
J Inorg Biochemjournal_title
Journal of inorganic biochemistryauthors
Cui H,Zhang AJ,McKeage MJ,Nott LM,Geraghty D,Guven N,Liu JJdoi
10.1016/j.jinorgbio.2017.04.022subject
Has Abstractpub_date
2017-12-01 00:00:00pages
249-258eissn
0162-0134issn
1873-3344pii
S0162-0134(17)30158-7journal_volume
177pub_type
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2005.10.010
更新日期:2006-01-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2003.09.012
更新日期:2004-01-01 00:00:00
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2012.02.020
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
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journal_title:Journal of inorganic biochemistry
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2014-02-01 00:00:00
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
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更新日期:2020-10-01 00:00:00
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章,评审
doi:10.1016/j.jinorgbio.2004.11.005
更新日期:2005-01-01 00:00:00
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2004.04.004
更新日期:2004-08-01 00:00:00
abstract::The peptide sequence PHSRN is the second cell binding site of the human fibronectin protein, a glycoprotein which plays a critical adhesive role during development, tissue repair and angiogenesis. The copper(II) complexes with the peptide fragment PHSRN were characterized by potentiometric and UV-visible, CD, EPR spec...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2012.04.002
更新日期:2012-08-01 00:00:00
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2007.06.024
更新日期:2007-10-01 00:00:00
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journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/0162-0134(84)80027-6
更新日期:1984-11-01 00:00:00