96P - CD146/Akt/NF-kappa-B/Latexin, a novel pathway suppressing breast tumor growth

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Breast Cancer
Translational Research
Presenter Ishita Gupta
Citation Annals of Oncology (2015) 26 (suppl_3): 31-33. 10.1093/annonc/mdv121
Authors I. Gupta1, A. Ouhtit2, A. Fernando2, Z. Abd Elmageed2, S. Shanmuganathan1
  • 1Genetics, Sultan Qaboos University, 123 - Muscat/OM
  • 2Genetics, Sultan Qaboos University, Al Khoud - Muscat/OM



While CD146 is a promoter of various tumor types, its function in breast cancer (BC) is still controversial. However, evidence from our work and others indicates that CD146 acts as a tumor suppressor in BC. To address this hypothesis, we developed both in vitro and in vivo tetracycline (tet On)-inducible system of CD146 using MDA-MB-231 founder BC cell line. Our results demonstrated that induction of CD146 suppressed BC cell migration and invasion in vitro as well as tumor growth and progression in a mouse breast xenograft model. Microarray gene expression profiling revealed latexin (LXN: a variant of Tissue Inhibitor of Metalloproteinases) as a novel potential CD146-downstream signaling transcriptional target, which was validated using various in vitro approaches. To further validate our findings in vivo, immunohistochemical analysis of breast tumor tissues from both human and mouse (tet-inducible system) breast tissues showed that while, the expression of both CD146 and LXN were highly expressed in the early stages of BC (normal and benign tissues), it was lost in advanced stages (malignant and metastatic tissues). To identify the main players involved in CD146-signaling pathway suppressing BC cell invasion, pharmacological approach combined with luciferase assay revealed that NFκB activation via Akt pathway couples CD146 to the transcription of LXN in BC CD146-inducible cells. Our findings support the hypothesis that CD146 is a breast tumor suppressor gene.

Disclosure: All authors have declared no conflicts of interest.