BRCA1 185delAG mutant protein, BRAt, up-regulates maspin in ovarian epithelial cells.

Objective: Aggressive clinical course and difficult detection of ovarian cancer are major challenges to improving patient survival and necessitate avid investigation into more effective therapeutic approaches. Understanding early molecular and pathological changes in high risk patients, such as BRCA1 mutation carriers, can provide candidates for molecular profiling and novel targets for effective therapies.

Methods: Using a culture model system for normal human ovarian surface epithelial cells with and without the BRCA1 185delAG frameshift mutation for the truncated protein product, BRAt, we investigated the role of BRAt in enhanced chemosensitivity.

BRCA1 185delAG truncation protein, BRAt, amplifies caspase-mediated apoptosis in ovarian cells.

Breast and ovarian cancer patients with germline mutations in BRCA1 respond more favorably to initial chemotherapy. We previously reported that cells from women carrying the BRCA1 185delAG founder mutation undergo an enhanced caspase-3-mediated apoptotic response. Here, we report on the transient and stable transfection of cDNA coding for the putative truncated protein product of the BRCA1 185delAG mutant gene into BRCA1 wild-type human ovarian surface epithelial cells and ovarian cancer cells, resulting in cells with a heterozygous background containing two BRCA1 wild-type alleles and the BRCA1 185delAG transcript.

MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN.

MicroRNAs (miRNA) represent a novel class of genes that function as negative regulators of gene expression. Recently, miRNAs have been implicated in several cancers. However, aberrant miRNA expression and its clinicopathologic significance in human ovarian cancer have not been well documented.