The role of BIG3 in onset/development mechanism of triple-negative breast cancer

2015 Fiscal Year Final Research Report

• Project/Area Number: 26893175
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokushima
• Principal Investigator: KIMURA Ryuichiro 徳島大学, 疾患プロテオゲノム研究センター, 特任助教 (20587323)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Keywords: 乳癌 / ゲノム / シグナル伝達 / プロテオーム / 発現制御

Outline of Final Research Achievements

We investigated the role of brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) in onset/development mechanism of estrogen receptor (ER)-negative breast cancers, including triple-negative breast cancer (TNBC). BIG3 was highly expressed in ER-negative breast cancer, as well as ER-positive cancer. Notably, BIG3 was strongly expressed in HER2-enriched breast cancer. A mechanism for BIG3 expression in ER-negative breast cancer was different from it in ER-positive breast cancer. High expression of BIG3 was associated with significantly shorter overall survival in both ER-positive and -negative cancer on public cohort. Knockdown of BIG3 expression with small-interfering RNA reduced cellular growths of human TNBC cell lines. Furthermore, we identified novel BIG3-interacting factors in breast cancer cells. These results demonstrate that BIG3 directly regulates cellular survival and growth of TNBC.

Free Research Field

腫瘍学