Characterization of functional messenger RNA splice variants of BRCA1 expressed in nonmalignant and tumor-derived breast cells.

BRCA1 has been identified as a tumor suppressor gene that is mutated in many cases of inherited breast and ovarian cancer. Recent data suggest that multiple splice forms of BRCA1 exist, but the structure and function of these alternative transcripts have not been elucidated. By sequence analysis of reverse transcription-PCR products, we have determined that a major splice form of BRCA1 expressed in malignant and nonmalignant breast epithelial cells contains an in-frame deletion of 3309 nucleotides from exon 11. A second alternative splice event results in the in-frame deletion of the 123 nucleotides that make up exons 9 and 10. These splice variants are found on polysomes and are therefore predicted to encode 80-85-kDa BRCA1-derived proteins lacking approximately 60% of the internal amino acids that constitute full-length BRCA1.

[1]  Z. Wang,et al.  Products of alternatively spliced transcripts of the Wilms' tumor suppressor gene, wt1, have altered DNA binding specificity and regulate transcription in different ways. , 1995, Oncogene.

[2]  David L. Page,et al.  Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progression , 1995, Nature Genetics.

[3]  M. Stampfer,et al.  Human mammary epithelial cells in culture: differentiation and transformation. , 1988, Cancer treatment and research.

[4]  J. Rossant,et al.  The Tumor Suppressor Gene Brca1 Is Required for Embryonic Cellular Proliferation in the Mouse , 1996, Cell.

[5]  D. Birnbaum,et al.  Truncation at conserved terminal regions of BRCA1 protein is associated with highly proliferating hereditary breast cancers. , 1996, Cancer research.

[6]  M. King,et al.  BRCA1 is secreted and exhibits properties of a granin , 1996, Nature Genetics.

[7]  Steven E. Bayer,et al.  A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. , 1994, Science.

[8]  C. Osborne,et al.  Location of BRCA1 in Human Breast and Ovarian Cancer Cells , 1996, Science.

[9]  J. Rubin,et al.  Hepatocyte Growth Factor (HGF)/NK1 Is a Naturally Occurring HGF/Scatter Factor Variant with Partial Agonist/Antagonist Activity* , 1996, The Journal of Biological Chemistry.

[10]  GROWTH RETARDATION AND TUMOUR INHIBITION BY BRCA1 , 1996 .

[11]  C. Osborne,et al.  Aberrant Subcellular Localization of BRCA1 in Breast Cancer , 1995, Science.

[12]  H. Nguyen,et al.  Hormone-dependent regulation of BRCA1 in human breast cancer cells. , 1995, Cancer research.

[13]  S. Atamas,et al.  An alternative splice variant of human IL-4, IL-4 delta 2, inhibits IL-4-stimulated T cell proliferation. , 1996, Journal of immunology.

[14]  H. Nguyen,et al.  Cell cycle regulation of BRCA1 messenger RNA in human breast epithelial cells. , 1996, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[15]  D. Goldman,et al.  Expression of Size‐Selected RNA Encoding Brain Serotonin Transporter in Xenopus laevis Oocytes , 1992, Journal of neurochemistry.

[16]  B. Koller,et al.  Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities , 1996, Nature Genetics.

[17]  C. Thompson,et al.  bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death , 1993, Cell.