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Reduced expression of SETD2 and SNX9 proteins in chemically induced mammary tumorigenesis in Wistar rats: a prognostic histological and proteomic study

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Abstract

Breast cancer is a major global health concern, appealing for precise prognostic approaches. Thus, the need is to have studies focusing on the identification and recognition of preliminary events leading to the disease. The present study reports the tracing of precancerous progression and serum proteomic analysis in a breast cancer model developed as a result of 7,12-dimethylbenz[a]anthracene (DMBA) administration. Mammary gland histological changes of prime importance were examined by histopathology, and immunohistochemical analysis with Ki-67 was performed to monitor enhanced cell proliferation, right from the onset of hyperplasia till neoplasia. Serum proteomics (one-dimensional (1D) and two-dimensional (2D) electrophoresis, followed by MALDI-TOF MS characterization) was performed to decipher the differentially expressed serum proteins in animals undergoing tumorigenesis vis-à-vis controls. The significance of our study lies in reporting the significantly reduced expression of two proteins: histone–lysine N-methyltransferase (SETD2) and sorting nexin-9 (SNX9) at very early stage (13 weeks) of tumorigenesis, while the full-fledged tumors developed after 6 months. The reduced expression of SETD2 and SNX9 was validated by western blotting and relative expression analysis using quantitative real-time PCR. These proteins may hence prove as potentially useful tools in search for prognostic markers for the early detection of mammary cancer.

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Acknowledgments

We are highly grateful to the University Grants Commission (UGC), India, for the financial support (F. No. 7-357/2011(BSR)) during this study. Further, the technical assistance provided by Dr. A K Tiwari (Veterinary Officer, Jamia Hamdard) and Dr. Prishla Varghese is also acknowledged.

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Authors and Affiliations

  1. Department of Biotechnology, Faculty of Science, Hamdard University (Jamia Hamdard), New Delhi, 110062, India

    Ishfaq Ahmad Ganaie & Saima Wajid

  2. Molecular Diagnostics, Genetix Biotech Asia, New Delhi, 110015, India

    Samar Husain Naqvi

  3. Department of Biochemistry, Hamdard Institute of Medical Sciences and Research, Hamdard University (Jamia Hamdard), New Delhi, 110062, India

    Swatantra Kumar Jain

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  1. Ishfaq Ahmad Ganaie
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Correspondence to Saima Wajid.

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The authors declare that they have no conflict of interest.

Funding

This study was funded by the University Grants Commission, India (grant number 7-357/2011(BSR)).

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures for using experimental animals were reviewed and approved (Approval ID/Project Number: 975) by the Institutional Animal Ethical Committee, accredited by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India.

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Handling editor: Jan Raoul De Mey

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Ganaie, I.A., Naqvi, S.H., Jain, S.K. et al. Reduced expression of SETD2 and SNX9 proteins in chemically induced mammary tumorigenesis in Wistar rats: a prognostic histological and proteomic study. Protoplasma 254, 1451–1466 (2017). https://doi.org/10.1007/s00709-016-1035-2

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