This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, M. Articles by Arrick, B. A. Search for Related Content PubMed Articles by Lu, M. Articles by Arrick, B. A.

Characterization of Functional Messenger RNA Splice Variants of BRCA1 Expressed in Nonmalignant and Tumor-derived Breast Cells¹

Departments of Medicine [B. A. A., S. D. C.] and Biochemistry [M. L., S. D. C., C. N. C.], and the Program in Molecular and Cellular Biology, Dartmouth Medical School, Hanover, New Hampshire 03755

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 This work was facilitated by the Dartmouth College Molecular Biology Core Facility, managed by Steve Bobin, and supported in part by the Cancer Center Support Grant CA-23108. S. D.C. was supported by a Howard Hughes Medical Institute Physician Post-doctoral Fellowship and the Hitchcock Foundation. B. A. A. is a recipient of a career development award from the U. S. Army (No. DAMD17-94-J-4130).

² To whom requests for reprints should be addressed, at Dartmouth Medical School, Kellogg Box 0128, Hanover, NH 03755. Phone: (603) 650-1550; Fax: (603) 650-1129; E-mail: Bradley.Arrick@dartmouth.edu.

Received 7/ 2/96. Accepted 8/27/96.

This article has been cited by other articles:

				F. Al-Mulla, M. Abdulrahman, G. Varadharaj, N. Akhter, and J. T. Anim BRCA1 Gene Expression in Breast Cancer: A Correlative Study between Real-time RT-PCR and Immunohistochemistry J. Histochem. Cytochem., May 1, 2005; 53(5): 621 - 629. [Abstract] [Full Text] [PDF]

				T I Orban and E Olah Emerging roles of BRCA1 alternative splicing Mol. Pathol., August 1, 2003; 56(4): 191 - 197. [Abstract] [Full Text] [PDF]

				J. L. Hilton, J. P. Geisler, J. A. Rathe, M. A. Hattermann-Zogg, B. DeYoung, and R. E. Buller Inactivation of BRCA1 and BRCA2 in Ovarian Cancer J Natl Cancer Inst, September 18, 2002; 94(18): 1396 - 1406. [Abstract] [Full Text] [PDF]

				M. Lu, E. A. Grove, and R. J. Miller Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor PNAS, May 14, 2002; 99(10): 7090 - 7095. [Abstract] [Full Text] [PDF]

				I. Bieche and R. Lidereau Increased Level of Exon 12 Alternatively Spliced BRCA2 Transcripts in Tumor Breast Tissue Compared with Normal Tissue Cancer Res., June 1, 1999; 59(11): 2546 - 2550. [Abstract] [Full Text] [PDF]

				F. Durocher, J. Simard, J. Ouellette, V. Richard, F. Labrie, and G. Pelletier Localization of BRCA1 Gene Expression in Adult Cynomolgus Monkey Tissues J. Histochem. Cytochem., September 1, 1997; 45(9): 1173 - 1188. [Abstract] [Full Text] [PDF]

				I.-S. Kim, D.-H. Kim, S.-M. Han, M.-U. Chin, H.-J. Nam, H.-P. Cho, S.-Y. Choi, B.-J. Song, E.-R. Kim, Y.-S. Bae, et al. Truncated Form of Importin alpha Identified in Breast Cancer Cell Inhibits Nuclear Import of p53 J. Biol. Chem., July 21, 2000; 275(30): 23139 - 23145. [Abstract] [Full Text] [PDF]