Abnormal expression of ATP1A1 and ATP1A2 in breast cancer

Breast cancer is the first in incidence and the second in death among all solid tumors occurring in women. The identification of molecular genetic abnormalities in breast cancer is important to improve the results of treatment. In the present study, we analyzed microarray data of breast cancer expression profiling (NCBI GEO database, accession GSE65194), focusing on Na +/K +-ATPase coding genes. We found overexpression of the ATP1A1 and down-regulation of the ATP1A2. We expect that our research could help to improve the understanding of predictive and prognostic features of breast cancer.


Introduction
Breast cancer is one of the most common and deadly female solid tumors 1 . According to reports from Perou et al. 2 , further confirmed by other investigators 3,4 , breast cancer is a highly molecularly heterogeneous disease. The identification of molecular genetic abnormalities in breast cancer is important to improve the results of treatment and, for instance, to reveal new targets for specific therapies. Recent studies based on original retrospective analysis of digitalis use in breast cancer patients have demonstrated the anticancer effect of cardiac glycosides 5 that directly inhibit Na + /K + -ATPase (NKA) activity. NKA signaling functions after interaction with cardiac glycosides were also shown 6 . It seems rational that expression of NKA might influence breast cancer prognosis.
NKA is a significant integral membrane protein. NKA's main function is the creation and maintenance of electrochemical gradients for sodium and potassium ions in the living cell. These gradients have critical importance for control of cell volume, osmolarity and resting potential 7,8 . The minimal functional NKA consists of two associated alpha-and beta-subunits. The catalytic alpha-subunit is responsible for conversion of ATP energy to transport of Na + and K + across cell membranes and has ATP and cardiac glycosides binding sites. It may be present in human tissues in four different isoforms (α1, α2, α3, α4 -found only in testicles). The beta-subunit is responsible for delivery and insertion of alpha one in cell membranes and has three distinct isoforms in humans (β1, β2, β3) 8-10 . NKA subunits are variably expressed in different human tissues 11 . Changes in the relative expression between different isoforms are associated with a number of pathological processes including malignant transformation 12,13 . Both down-and up-regulation of alpha-and beta-subunits were shown in solid tumors of different origin 14-19 .
In the present study, we analyzed public breast cancer expression profiles made using Affymetrix Human Genome U133 Plus 2.0 Array (NCBI GEO database 20 , accession GSE65194) for the expression of alpha subunits of NKA. We found abnormalities in ATP1A1 (coding α1-subunit) and ATP1A2 (coding α2-subunit) expression (

Conclusions
Using a public microarray dataset we found abnormalities in the expression of ATP1A1 and ATP1A2 in breast cancer samples. This may correlate with digitalis anticancer activity, but requires additional research. We expect that our research could help to improve the understanding of predictive and prognostic features of breast cancer.

Data and software availability
Raw data for Table 1  Author contributions AB, FM and MD conceptualized the study, collected data and performed data analysis. All authors were involved in the writing and revision of the draft manuscript and have agreed to the final content.

Competing interests
No competing interests were disclosed.

Grant information
This work was supported by The Ministry of Education and Science of Russian Federation (unique identifier of applied research: RFMEFI60414X0070). I would like to note that the authors studied gene expression only, but did not appreciate the immunohistochemical (IHC) changes in the content of gene products. In the absence of data of the IHC expression of , it is desirable to represent the differences in gene expression of ATP1A1 ATP1A1 compared to referent genes for membrane transporters ( ). Given a sufficiently large http://bmcmolbiol.biomedcentral.com/articles/10.1186/1471-2199-7-29 number of patients included in the study, it is interesting to evaluate the prognostic and predictive value of these findings. But I can conclude that this article is interesting for medical oncologists and molecular biologists.
No competing interests were disclosed.

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