Cell lines:
- BRCA2 expression is regulated by estrogens in human breast cancer cell lines (Spillman M.A. and Bowcock A.M., 1996).
Tumors:
- Somatic BRCA2 gene mutations have been detected only exceptionally (Teng D.H.F. et al., 1996).
-
Progesterone receptor and
cyclin D expression was found lower in
BRCA1 and BRCA2-associated (familial) breast cancers than in sporadic cancers. No difference was found for the
estrogen receptor and
pS2 (Osin P. et al., 1998).
- Loss of heterozygosity (LOH) was found in the BRCA1 region in 47/108 (44%) breast tumors. LOH in this region was significantly correlated to age <=50, lymph node metastase >3,
estrogen receptor negativity,
progesterone receptor negativity, higher histologic grade, higher stage, and peritumoral vessel involvement (Gonzalez R. et al., 1999).
- A BRCA2 splice variant lacking exon 12 has been described in both normal and tumor breast tissue. Its expression was higher in tumor tissue than in normal tissue, especially (P=0.0005) in steroid receptor-negative tumors. The deletion observed in this transcript (96 bp) preserves the open reading frame, and translation of the transcript would result in a BRCA2 isoform lacking 32 amino acids between codons 2280 and 2311 (Bièche I. and Lidereau R., 1999).
- BRCA2 mRNA was quantified by means of RT-PCR in a large series of human primary breast tumours. BRCA2 expression showed wide variations in tumour tissues, being underexpressed in 14/127 (11%) and overexpressed in 25/127 (20%). BRCA2 overexpression (but not underexpression) correlated significantly with Scarff, Bloom and Richardson (SBR) histopathological grade III (P=0.007) and was mainly attributed to nuclear polymorphism (P=0.005) and mitotic index (P=0.048), suggesting that the BRCA2 gene contributes to the proliferation rate in breast tumours. BRCA2 status (under and/or overexpression versus normal expression) was not associated with subsequent relapse and with significantly shorter disease-free survival. The observed disruption of BRCA2 expression is not due to allelic loss, because the latter did not correlate with altered BRCA2 mRNA expression in our tumour series (Bièche I. et al., 1999).
Bièche I. and Lidereau R. (1999) Increased level of exon 12 alternatively spliced BRCA2 transcripts in tumor breast tissue compared with normal tissue. Cancer Res. 59, 2546-2550.
Bièche I. et al.(1999) Overexpression of BRCA2 gene in sporadic breast tumours. Oncogene 18, 5232-5238.
Chen J. et al. (1998) Stable interaction between the products of the
BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Molec. Cell 2, 317-328.
Gonzales R. et al. (1999) Detection of loss of heterozygosity at RAD51, RAD52, RAD54 and
BRCA1 and BRCA2 loci in breast cancer: pathological correlations. Br. J. Cancer 81, 503-509.
Osin P. et al. (1998) Predicted anti-oestrogen resistance in
BRCA-associated familial breast cancers. Eur. J. Cancer 34, 1683-1686.
Spillman M.A. and Bowcock A.M. (1996)
BRCA1 and BRCA2 mRNA are coordinately elevated in human breast cancer cells in response to estrogen. Oncogene 13, 1639-1645.
Teng D.H.F. et al. (1996) Low incidence of BRCA2 mutations in breast carcinoma and other cancers. Nature Genet. 13, 241-244.
Wooster R. et al. (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 265, 2088-2090.
Wooster R. et al. (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378, 789-792.
