Get access
Journal of Cellular Biochemistry

Alterations in replication timing of cancer-related genes in malignant human breast cancer cells

Authors

  • Andrew Fritz,

    1. Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, New York 14260
    Search for more papers by this author
  • Seema Sinha,

    1. Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, New York 14260
    Current affiliation:
    1. Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232.
    Search for more papers by this author
  • Narasimharao Marella,

    1. Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, New York 14260
    Current affiliation:
    1. Cancer Genetics, Inc., Rutherford, NJ 07070.
    Search for more papers by this author
  • Ronald Berezney

    Corresponding author
    1. Department of Biological Sciences, University at Buffalo, State University of New York, Buffalo, New York 14260
    • Department of Biological Sciences, University at Buffalo, Buffalo, NY 14260.
    Search for more papers by this author

  • This article is dedicated to Professor Donald S. Coffey at The Johns Hopkins University School of Medicine on the occasion of his 80th birthday.

Abstract

The replication timing of nine genes commonly involved in cancer was investigated in the MCF10 cell lines for human breast cancer progression. Six of these nine genes are part of a constellation of tumor suppressor genes that play a major role in familial human breast cancer (TP53, ATM, PTEN, CHK2, BRCA1, and BRCA2). Three other genes are involved in a large number of human cancers including breast as either tumor suppressors (RB1 and RAD51) or as an oncogene (cMYC). Five of these nine genes (TP53, RAD51, ATM, PTEN, and cMYC) show significant differences (P < 0.05) in replication timing between MCF10A normal human breast cells and the corresponding malignant MCF10CA1a cells. These differences are specific to the malignant state of the MCF10CA1a cells since there were no significant differences in the replication timing of these genes between normal MCF10A cells and the non-malignant cancer MCF10AT1 cells. Microarray analysis further demonstrated that three of these five genes (TP53, RAD51, and cMYC) showed significant changes in gene expression (≥2-fold) between normal and malignant cells. Our findings demonstrate an alteration in the replication timing of a small subset of cancer-related genes in malignant breast cancer cells. These alterations partially correlate with the major transcriptional changes characteristic of the malignant state in these cells. J. Cell. Biochem. 114: 1074–1083, 2013. © 2012 Wiley Periodicals, Inc.

Get access to the full text of this article

Ancillary