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Functional identification of a BAC clone from 16q24 carrying a senescence gene SEN16 for breast cancer cells

Oncogene volume 24, pages 47–54 (2005)Cite this article

Abstract

We have identified an 85 kb BAC clone, 346J21, that carries a cell senescence gene (SEN16), previously mapped to 16q24.3. Transfer and retention of 346J21 in breast cancer cell lines leads to growth arrest after 8–10 cell doublings, accompanied by the appearance of characteristic senescent cell morphology and senescence-associated acid β-galactosidase activity. Loss of transferred BAC results in reversion to the immortal growth phenotype of the parental cancer cell lines. BAC 346J21 restores senescence in the human breast cancer cell lines, MCF.7 and MDA-MB468, and the rat mammary tumor cell line LA7, but not in the human glioblastoma cell line T98G. We postulate that inactivation of both copies of SEN16 is required for the immortalization of breast epithelial cells at an early stage of tumorigenesis. Positional mapping of 346J21 shows that SEN16 is distinct from other candidate tumor suppressor genes reported at 16q24.

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Acknowledgements

This work was supported in part by a grant to GPK from the American Cancer Society (ACS# RPG-97-138-01-MGO), and grants to RSA from the Susan G Komen Breast Cancer Foundation (#9830) and NIH (CA74983). DER was supported by a predoctoral fellowship from US Army Breast Cancer Research Program (DAMD# 17-96-1-6059).

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Authors and Affiliations

  1. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, 19140, USA

    Gursurinder Pal Kaur, Deepthi E Reddy, Jon K de Riel & Raghbir S Athwal

  2. Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, MD, 20892, USA

    Drazen B Zimonjic

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  1. Gursurinder Pal Kaur
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  2. Deepthi E Reddy
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  3. Drazen B Zimonjic
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Correspondence to Gursurinder Pal Kaur.

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Kaur, G., Reddy, D., Zimonjic, D. et al. Functional identification of a BAC clone from 16q24 carrying a senescence gene SEN16 for breast cancer cells. Oncogene 24, 47–54 (2005). https://doi.org/10.1038/sj.onc.1208175

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