Germ‐line mutations in BRCA1 or BRCA2 in the normal breast are associated with altered expression of estrogen‐responsive proteins and the predominance of progesterone receptor A

• DOI: 10.1002/gcc.10321
• Publication Date: 2004-01-15T10:01:18Z
• Authors: Patricia A. Mote; Jennifer A. Leary; Kelly A. Avery; Kerstin Sandelin; Georgia Chenevix‐...; Judy A. Kirk; Christine L. Clarke
• Keywords: Progesterone receptor

The breast cancer susceptibility genes BRCA1 and BRCA2 are responsible for a large proportion of familial ovarian cancer, yet little is known how disruptions in the functions proteins these encode increased risk preferentially hormone-dependent tissue. There no information on whether germ-line mutation or causes hormone-signaling pathways normal breast. In this study markers hormone responsiveness were measured prophylactically removed tissue (n = 31) women bearing pathogenic one BRCA genes. estrogen receptor (ER) associated with ER action hormone-sensitive tissues, namely, PS2 progesterone (PR), detected immunohistochemically. expression was not different carriers than noncarriers, but there reduction expression. PR also reduced, striking lack PRB isoform, which resulted cases PRA-only carriers. alterations similar carriers, demonstrating that although structurally functionally distinct, overlap their interaction pathways. This provides evidence altered cell function arising from loss allele breast, leading to loss, preferential PRA alone. development, overexpression becomes evident premalignant lesions features poor prognosis invasive disease vitro. results suggest heterozygosity development predominance. likely lead changes signaling may be factor tissues mutations.