Both nuclear and cytoplasmic beta-catenin expressions were demonstrated in 4 of the 27 ovarian carcinomas for which tissue samples were available for examination.
Of 37 families containing more than two ovarian cancer cases and at least one breast cancer case with diagnosis at less than 60 years of age, 30 (81%) had a BRCA1/2 mutation.
Four additional missense variants (one in BRCA1 and three in BRCA2) with a possible association with an increased risk ovarian cancer were revealed, resulting in a total frequency of BRCA gene alterations of 17/161 (11%).
BRCA1 abnormalities were identified in all four families with ovarian cancer only, in 67% of 27 families with both breast and ovarian cancer, and in 34% of 35 families with breast cancer only.
Our data support a tumour suppressor mechanism for BRCA1; somatic mutations and LOH may result in inactivation of BRCA1 in at least a small number of ovarian cancers.
Importantly, we found that ΔNp63α, AKT1, and phospho-AKT levels are greater in 2008CI3 CDDP-resistant ovarian cancer cells than in 2008 CDDP-sensitive cells. siRNA-mediated knockdown of ΔNp63α expression dramatically decreased AKT1 expression, whereas knockdown of either ΔNp63α or AKT1 decreased cell proliferation and increased death of ovarian and head/neck cancer cells.
Ovarian tumors from heterozygous carriers of the Icelandic mutation show loss of the wild-type allele, indicating that BRIP1 behaves like a classical tumor suppressor gene in ovarian cancer.
Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma.