BRCA1 Mutations Influence Cancer Cells’ Response to Drugs
November 20, 2007
JNCI publish study by Queen’s University Belfast and Almac Diagnostic Services
The Journal of the National Cancer Institutes has published results of a collaboration between Queens University, Belfast and Almac Diagnostic Services using the company’s Breast Cancer Disease Specific Array™, to generate valuable new insight into the interactions between BRCA1 and estrogen receptor alpha (ERα).
It has been widely reported in the literature that BRCA1 linked breast cancers typically fail to express ERα, however the mechanism behind this link has remained obscure. ERα is the therapeutic target for antiestrogen therapies such as fulvestrant and tamoxifen, while BRCA1, a tumour suppressor gene, is associated with genetic predisposition to breast and ovarian cancers.
The Queens / Almac study has demonstrated that BRCA1 alters the response of breast cancer cells to fulvestrant therapy by directly modulating ERα mRNA expression.
“The initial clue that BRCA1 may directly regulate ERα at the mRNA level came from expression profiling studies utilizing the Almac Diagnostic Services Breast Cancer DSATM directly from Formalin Fixed Paraffin Embedded (FFPE) tumour samples,” said Prof Paul Harkin.
The array data demonstrated that ERα mRNA expression was 5.4-fold lower in tumors with BRCA1 mutations than in sporadic tumors and was subsequently confirmed by real time PCR. The study went on to demonstrate that BRCA1 directly regulates ESR1 expression through an Oct-1 dependent interaction with the ESR1 promoter. Finally it was shown that expression of ERα in BRCA1-depleted breast cancer cells made the cells more sensitive to an antiestrogen drug Fulvestrant. They conclude that BRCA1 alters the response of breast cancer cells to antiestrogen therapy by directly influencing ERα expression.
For further information, please contact Kerry Kennedy,