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Suppression of ING1 expression in sporadic breast cancer

Oncogene volume 18, pages 5187–5193 (1999)Cite this article

Abstract

Down regulation of the ING1 candidate tumour suppressor promotes growth in soft agar and focus formation in vitro and tumour formation in vivo. ING1 encodes a nuclear, cell cycle-regulated protein, overexpression of which efficiently blocks cell growth and is capable of inducing apoptosis in different experimental systems. Here we present the first report of ING1 mutation and expression analysis in a total of 452 cancer samples. One germline missense alteration and three germline silent alterations were detected in 377 primary breast cancers while marked (2 – 10-fold) decreases in ING1 mRNA expression were seen in 44% of primary breast cancers and in ten of ten breast cancer cell lines examined. Furthermore, the majority of breast cancers (58%) showing decreased ING1 expression had metastasized to regional lymph nodes whereas only 9% of cancers with elevated ING1 expression, compared to adjacent normal tissues, were metastatic. Thus, ING1 mutation is very rare in breast or ovarian cancers, however, repression of ING1 expression frequently accompanies tumour development of breast cancer.

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Abbreviations

PCR – SSCP:

polymerase chain reaction-single strand conformation polymorphism

RT:

reverse transcription

DCIS:

ductal carcinoma in situ

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

DAB:

3, 3′ diaminobenzidine

NBT/BCIP:

nitroblue tetrazolium chloride/5-bromo-4-chloro-3-idolyl-phosphate, 4-toluidine salt

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Acknowledgements

We thank Dr D Fujita for providing breast cancer cell lines, Drs RN Johnston and D Edwards for critical and insightful comments and D Boland and the SACRC Hybridoma Facility for antibody production. This work was supported by grants from the Alberta Cancer Board, the Alberta Breast Cancer Foundation/Honda Run for the Cure, and the National Cancer Institute of Canada to Karl Riabowol. The NCIC-Manitoba Breast Tumour Bank is supported by the National Cancer Institute of Canada.

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Author notes

  1. Igor Garkavtsev

    Present address: Genome Therapeutics Inc., 100 Beaver Street, Waltham, MA 02154-8440, Massachusetts, USA

Authors and Affiliations

  1. Departments of Biochemistry & Molecular Biology and Oncology and Southern Alberta Cancer Research Centre, Faculty of Medicine, The University of Calgary, 3330 Hospital Drive, NW, Calgary, T2N 4N1, Alberta, Canada

    Tatsuya Toyama, Elizabeth Saettler, Igor Garkavtsev & Karl Riabowol

  2. Department of Clinical Neuroscience, Faculty of Medicine, The University of Calgary, 3330 Hospital Drive, NW, Calgary, T2N 4N1, Alberta, Canada

    Huong Muzik & Peter Forsyth

  3. Department of Surgery II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Hirotaka Iwase & Shunzo Kobayashi

  4. Department of Pathology, Faculty of Medicine, The University of Manitoba, D212-770 Bannatyne Avenue, Winnipeg, R3E 0W3, Manitoba, Canada

    Peter Watson

  5. Department of Pathology, College of Medicine, The University of Saskatchewan, Royal University Hospital, 103 Hospital Drive, Saskatoon, S7N 0W8, Saskatchewan, Canada

    Anthony Magliocco

  6. Department of Pathology, Foothills Hospital, 1403 – 29 Street, NW, Calgary, T2N 2T9, Alberta, Canada

    Lisa DiFrancesco

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Toyama, T., Iwase, H., Watson, P. et al. Suppression of ING1 expression in sporadic breast cancer. Oncogene 18, 5187–5193 (1999). https://doi.org/10.1038/sj.onc.1202905

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  • DOI: https://doi.org/10.1038/sj.onc.1202905

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