Differential subcellular localization, expression and biological toxicity of BRCA1 and the splice variant BRCA1-Δ11b (original) (raw)

• Original Paper
• Published: 09 January 1997
• Marc N Payton2,
• Gary S Elliott2,
• F William Buaas2,
• Elaina E Cajulis2,
• David Grosshans2,
• Lillian Ramos3,
• David M Reese3,
• Dennis J Slamon3 &
• …
• Frank J Calzone2

Oncogene volume 14, pages 1–16 (1997)Cite this article

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Abstract

The mechanism of BRCA1 tumor suppression in human breast and ovarian cells is the focus of intense investigation. In this report, full length BRCA1 (230 kDa) introduced into cells with CMV promoter constructs was nuclear when transgene expression was low whereas high expression resulted in cytoplasmic accumulation, aberrant nuclear and cell morphology. A nuclear localization signal (NLS) was mapped to BRCA1 amino acid positions 262 – 570. We describe a splice variant, BRCA1-Δ11b, missing the majority of exon 11 including the NLS. Exogenous BRCA1-Δ11b (110 kDa) was cytoplasmic and, unlike the full-length protein, overexpression of the protein encoded by the variant did not appear to be toxic. RNA probe titrations and RT – PCR demonstrated that BRCA1 and Δ11b transcripts are coexpressed in a wide variety of cells and tissues. Interestingly, BRCA1-Δ11b message was greatly reduced or absent in several breast and ovarian tumor lines relative to exon 11 transcripts and a Δ9,10 splice variant. Taken together our results suggest that full-length BRCA1 and BRCA1-Δ11b may have distinct roles in cell growth regulation and tumorigenesis.

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Authors and Affiliations

1. Developmental and Cell Biology, University of California, Irvine, 92717, California, USA
   Cindy A Wilson
2. Molecular Biology, Amgen Inc, Amgen Center, Thousand Oaks, 91320, California, USA
   Marc N Payton, Gary S Elliott, F William Buaas, Elaina E Cajulis, David Grosshans & Frank J Calzone
3. Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles, 90095, California, USA
   Lillian Ramos, David M Reese & Dennis J Slamon

Authors

1. Cindy A Wilson
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2. Marc N Payton
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3. Gary S Elliott
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4. F William Buaas
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5. Elaina E Cajulis
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6. David Grosshans
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7. Lillian Ramos
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8. David M Reese
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9. Dennis J Slamon
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10. Frank J Calzone
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Wilson, C., Payton, M., Elliott, G. et al. Differential subcellular localization, expression and biological toxicity of BRCA1 and the splice variant BRCA1-Δ11b.Oncogene 14, 1–16 (1997). https://doi.org/10.1038/sj.onc.1200924

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• Received: 07 August 1996
• Revised: 31 October 1996
• Accepted: 31 October 1996
• Issue Date: 09 January 1997
• DOI: https://doi.org/10.1038/sj.onc.1200924

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