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cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype

Oncogene volume 18, pages 6063–6070 (1999)Cite this article

Abstract

We have previously demonstrated decreased Jun/AP-1 activity in the breast cancer cell line MCF-7 when compared to normal or immortalized mammary epithelial cells. In this paper, we overexpress Jun in MCF-7 cells (MCF7Jun) and demonstrate that it results in diverse biologic and biochemical changes, which mimic those seen clinically in breast cancer. Overexpression of Jun causes significant alterations in the composition of AP-1, decreased junB and increased fra-1 expression and results in an increased biologic aggressiveness. MCF7Jun cells exhibit increased cellular motility, increased expression of a matrix degrading enzyme MMP-9, increased in vitro chemoinvasion and tumor formation in nude mice in the absence of exogenous estrogens. Furthermore, MCF7Jun cells are unresponsive to the growth stimulating effects of estrogen and growth inhibitory effects of tamoxifen. Analysis of the estrogen receptor (ER) expression and activity showed that the MCF7Jun cells have no detectable ER. MCF-7 cells overexpressing mutant forms of cJun were responsive to the growth stimulatory effects of estrogen indicating that full-length cJun is required to acquire the estrogen-independent phenotype in breast cancer cells.

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Acknowledgements

LM Smith and SC Wise are co-first authors for this study. We thank Dr M Karin and Dr P Chambon for their generous gifts of plasmids. We also thank Amy Guzzone for her technical expertise.

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Author notes

  1. Leia M Smith

    Present address: Department of Radiological Health Sciences, Colorado State University, Fort Collins, Colorado, CO 80523, USA

  2. Scott C Wise

    Present address: Department of Cell Biology, Parke-Davis Research, Ann Arbor, Michigon, MI 48105, USA

  3. Anita L Sabichi

    Present address: Departments of Clinical Cancer Prevention and Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, TX 77030, USA

  4. Anita L Sabichi

    Present address: Department of Digestive Diseases, University of Texas, MD Anderson Cancer Center, Houston, Texas, TX 77030, USA

Authors and Affiliations

  1. Department of Cell and Cancer Biology, Medicine Branch, National Cancer Institute, NIH, Rockville, 20850, Maryland, MD, USA

    Leia M Smith, Scott C Wise, Denver T Hendricks, Anita L Sabichi & Michael J Birrer

  2. Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk, 2350, Virginia, VA, USA

    Timothy Bos

  3. Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, 78284, Texas, TX, USA

    Praveen Reddy & Powel H Brown

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Smith, L., Wise, S., Hendricks, D. et al. cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype. Oncogene 18, 6063–6070 (1999). https://doi.org/10.1038/sj.onc.1202989

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