These results suggest that BRCA1 may be a potential regulator of EGFR in ovarian cancer, although a similar phenomenon has even been observed in breast cancer. It appears that BRCA1 rather than BRCA2 may be a potential regulator of EGFR expression. In agreement with these findings, Nisman suggested that the concentration of soluble EGFR was significantly higher in women with BRCA1 mutations than in controls and women with BRCA2 mutations. Interestingly, the activation effect due to the loss of BRCA1 was primarily observed in cells originating from ovarian cancer, while 293 T cells were insensitive to the overexpression or knockdown of BRCA1. Hence, the induced expression of EGFR was likely to be the result of a complex interaction of special factors in ovarian can cer cells.

Notably, several studies suggest that BRCA1 haploinsufficiency is more likely to become cancerous compared with the non BRCA1 mutated kinase inhibitor FH535 group, due to an extraordinary ability for clonal growth and prolifera tion. EGFR also plays an important role in regulat ing cell proliferation and resistance to cell apoptosis during cancer development. As shown in Additional file 2, BRCA1 knockdown mediated EGFR overexpression is associ ated with increased proliferation, and proliferative ef fects were reversed by the EGFR inhibitor erlotinib. Moreover, patients with low BRCA1 related high levels of EGFR showed a trend for poor survival. Therefore, it can be predicted that BRCA1 inactivation related high levels of EGFR may be involved in promoting ovarian cancer progression.

To date, it is not fully understood how BRCA1 represses EGFR gene expres sion at the molecular level. However, is it possible that the repression takes place at the transcriptional level Some insight was gained by a study demonstrating PTC-209 HBr concentration that BRCA1 is an important transcriptional regulator, which modulates the translational efficiency of approximately 7% of the mRNAs expressed in human breast cancer cell line MCF 7. A growing body of evidence suggests that BRCA1 has extensive cellular effects on hormone receptor signaling pathways. For example, BRCA1 can inhibit progesterone receptor activity in the PR positive human breast cancer cell line T47D and repress estrogen receptor alpha activity in MCF 7 cells. BRCA1 may also be a potential regulator of the insulin like growth factor 1 receptor in human breast cancer cell line HCC1937. However, to date, there have been few reports about the interactions between BRCA1 and EGFR in ovarian cancer.