. For women in the United States, epithelial ovarian cancer is the second most common gynecological cancer and a leading cause of death. Women who carry mutations in the BRCA1 gene are at a high risk for development of sporadic ovarian cancers. In these cancers, BRCA1 dysfunction is common, and silencing of genes in the BR(iA1 pathway is apparently involved in their development. BRCA1 and its isoform, BRCA1a, are nuclear-cytoplasm shuttling proteins, tDut the trafficking pathway that is deregulated in ovarian cancers, resulting in cytoplasmic localization of BRCA1, is currently unknown. We have found that wild-type nuclear BRCA1 and BRCA1a proteins inhibit growth of ovarian cancer cells;these proteins bind the nuclear chaperone, Ubc9, and degrade ER-alpha. In contrast, BRCA1/BRCA1a proteins with a cancer-causing C61G mutation or with the Ubc9 binding-site K109R mutation are mis-localized to the cytoplasm and have impaired capacity to inhibit growth of these cells. HYPOTHESIS: Based on these preliminary results, we hypothesize that BRCA1, by binding to Ubc9, functions as a tumor suppressor and thereby inhibits growth of ovarian tumors. For BRCA1 dysfunction, as seen in BRCA1-associated hereditary (genetic) and sporadic ovarian cancers (post-translational modifications), there is disrupted interaction with Ubc9, causing cytoplasmic retention of BRCA1 proteins and deregulated Ubc9 levels, resulting in ovarian cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA118948-08
Application #
8759625
Study Section
Special Emphasis Panel (ZCA1-SRLB-Y (O1))
Project Start
2005-09-30
Project End
2016-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
8
Fiscal Year
2013
Total Cost
$24,297
Indirect Cost
$7,512
Name
University of Alabama Birmingham
Department
Type
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Tabatabai, Mohammad A; Kengwoung-Keumo, Jean-Jacques; Oates, Gabriela R et al. (2016) Racial and Gender Disparities in Incidence of Lung and Bronchus Cancer in the United States: A Longitudinal Analysis. PLoS One 11:e0162949
Akinyemiju, Tomi; Meng, Qingrui; Vin-Raviv, Neomi (2016) Association between body mass index and in-hospital outcomes: Analysis of the nationwide inpatient database. Medicine (Baltimore) 95:e4189
Wang, Honghe; Liu, Wei; Black, ShaNekkia et al. (2016) Kaiso, a transcriptional repressor, promotes cell migration and invasion of prostate cancer cells through regulation of miR-31 expression. Oncotarget 7:5677-89
Fouad, Mona N; Acemgil, Aras; Bae, Sejong et al. (2016) Patient Navigation As a Model to Increase Participation of African Americans in Cancer Clinical Trials. J Oncol Pract 12:556-63
Kamal, Arif H; Dionne-Odom, J Nicholas (2016) A Blue Ocean Strategy for Palliative Care: Focus on Family Caregivers. J Pain Symptom Manage 51:e1-3
Li, Rong; Zhang, Kui; Penedo, Thuy Linh et al. (2016) The RANK Pathway in Advanced Breast Cancer: Does Src Play a Role? Appl Immunohistochem Mol Morphol 24:42-50
Dionne-Odom, J Nicholas; Hull, Jay G; Martin, Michelle Y et al. (2016) Associations between advanced cancer patients' survival and family caregiver presence and burden. Cancer Med 5:853-62
Okwali, Michelle; Greenlee, Heather; Ginindza, Themba et al. (2016) Adherence to cancer prevention guidelines in South Africa is associated with health care access. Int Health 8:211-9
Costas, Laura; Lambert, Brice H; Birmann, Brenda M et al. (2016) A Pooled Analysis of Reproductive Factors, Exogenous Hormone Use, and Risk of Multiple Myeloma among Women in the International Multiple Myeloma Consortium. Cancer Epidemiol Biomarkers Prev 25:217-21
Jones, Jacqueline; Mukherjee, Angana; Karanam, Balasubramanyam et al. (2016) African Americans with pancreatic ductal adenocarcinoma exhibit gender differences in Kaiso expression. Cancer Lett 380:513-22

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