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Amplification and overexpression of the ABCC3 (MRP3) gene in primary breast cancer

Partanen, Laura; Staaf, Johan LU ; Tanner, Minna; Tuominen, Vilppu J.; Borg, Åke LU and Isola, Jorma (2012) In Genes, Chromosomes and Cancer 51(9). p.832-840
Abstract
The ATP-binding cassette (ABC) of active transporters comprises a group of proteins that which facilitate efflux of anticancer drugs from cancer cells. We focused on the gene amplification and protein expression of ABCC3 (also known as MRP3) in breast cancer cell lines and clinical tumor samples. Fluorescence and chromogenic in situ hybridization, using an ABCC3-specific probe, was used to analyze 11 breast cancer cell lines and 112 clinical tumor samples. The results of ABCC3 were correlated with the amplification status of HER2 and topoisomerase II alpha (TOP2A), which are located close to ABCC3 at 17q12-q21. Immunohistochemistry was used to assess ABCC3 protein overexpression. Of the cell lines studied 6 HER2-positive lines and 1... (More)
The ATP-binding cassette (ABC) of active transporters comprises a group of proteins that which facilitate efflux of anticancer drugs from cancer cells. We focused on the gene amplification and protein expression of ABCC3 (also known as MRP3) in breast cancer cell lines and clinical tumor samples. Fluorescence and chromogenic in situ hybridization, using an ABCC3-specific probe, was used to analyze 11 breast cancer cell lines and 112 clinical tumor samples. The results of ABCC3 were correlated with the amplification status of HER2 and topoisomerase II alpha (TOP2A), which are located close to ABCC3 at 17q12-q21. Immunohistochemistry was used to assess ABCC3 protein overexpression. Of the cell lines studied 6 HER2-positive lines and 1 HER2-negative line exhibited amplification of ABCC3. In the HER-2-negative clinical tumor samples, only 4/55 (7.3%) exhibited ABCC3 amplification. In the HER2-positive tumors, ABCC3 was amplified in 16/57 tumors (28.1%, P = 0.0059). TOP2A did not exhibit any consistent coamplification pattern. ABCC3 (MRP3) protein overexpression was more common in tumors with gene amplification (P = 0.069). In silico analysis of 804 breast cancers with matched gene expression and copy number microarray data revealed significant differences ABCC3 across the molecular subtypes. Specifically, increased ABCC3 mRNA and gene copy numbers were most prominent in HER2 amplified and/or HER2-enriched classified tumors. Moreover, differential ABCC3 mRNA levels were found within the HER-2 amplified subset when stratified by the estrogen receptor status. We conclude that ABCC3 is frequently amplified and overexpressed in HER2-positive breast cancer, and something that warrants further studies correlating the results with therapeutic outcome. (C) 2012 Wiley Periodicals, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
51
issue
9
pages
832 - 840
publisher
John Wiley & Sons
external identifiers
  • wos:000306139900002
  • scopus:84863565481
ISSN
1045-2257
DOI
10.1002/gcc.21967
language
English
LU publication?
yes
id
fcfd3673-3f5a-4607-9e55-8ee815e60afd (old id 2994813)
date added to LUP
2012-09-03 07:17:49
date last changed
2017-07-02 03:01:44
@article{fcfd3673-3f5a-4607-9e55-8ee815e60afd,
  abstract     = {The ATP-binding cassette (ABC) of active transporters comprises a group of proteins that which facilitate efflux of anticancer drugs from cancer cells. We focused on the gene amplification and protein expression of ABCC3 (also known as MRP3) in breast cancer cell lines and clinical tumor samples. Fluorescence and chromogenic in situ hybridization, using an ABCC3-specific probe, was used to analyze 11 breast cancer cell lines and 112 clinical tumor samples. The results of ABCC3 were correlated with the amplification status of HER2 and topoisomerase II alpha (TOP2A), which are located close to ABCC3 at 17q12-q21. Immunohistochemistry was used to assess ABCC3 protein overexpression. Of the cell lines studied 6 HER2-positive lines and 1 HER2-negative line exhibited amplification of ABCC3. In the HER-2-negative clinical tumor samples, only 4/55 (7.3%) exhibited ABCC3 amplification. In the HER2-positive tumors, ABCC3 was amplified in 16/57 tumors (28.1%, P = 0.0059). TOP2A did not exhibit any consistent coamplification pattern. ABCC3 (MRP3) protein overexpression was more common in tumors with gene amplification (P = 0.069). In silico analysis of 804 breast cancers with matched gene expression and copy number microarray data revealed significant differences ABCC3 across the molecular subtypes. Specifically, increased ABCC3 mRNA and gene copy numbers were most prominent in HER2 amplified and/or HER2-enriched classified tumors. Moreover, differential ABCC3 mRNA levels were found within the HER-2 amplified subset when stratified by the estrogen receptor status. We conclude that ABCC3 is frequently amplified and overexpressed in HER2-positive breast cancer, and something that warrants further studies correlating the results with therapeutic outcome. (C) 2012 Wiley Periodicals, Inc.},
  author       = {Partanen, Laura and Staaf, Johan and Tanner, Minna and Tuominen, Vilppu J. and Borg, Åke and Isola, Jorma},
  issn         = {1045-2257},
  language     = {eng},
  number       = {9},
  pages        = {832--840},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Amplification and overexpression of the ABCC3 (MRP3) gene in primary breast cancer},
  url          = {http://dx.doi.org/10.1002/gcc.21967},
  volume       = {51},
  year         = {2012},
}