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conferenceseries
.com
Volume 2, Issue 4 (Suppl)
Breast Can Curr Res, an open access journal
Breast Pathology 2017
August 23-24, 2017
August 23-24, 2017 Toronto, Canada
4
th
World Congress on
Breast Pathology and Cancer Diagnosis
Role of PI3K/AKT-signaling pathway in triple-negative breast cancer
J C Hahne, A Lampis, S R Meyer, A Honig, J B Engel
and
N Valeri
The institute of Cancer Research, Russia
B
reast cancer accounts for 23% of all new tumor cases and it is the most common cancer among women worldwide.
A high percentage (15-25% of all breast cancer cases) is characterized as triple-negative breast cancer (TNBC).
Although triple-negative cancers are sensitive to chemotherapy, survival of patients with these tumors is poor. Lack
of effective therapies, younger age at onset and early metastatic spread have contributed to the poor prognosis and
outcomes associated with TNBC. The phosphatidylinositol 3-kinase (PI3K)/ AKT-pathway plays a critical role in
malignant transformation of tumors and their subsequent growth, proliferation and metastasis as well as in activation
of pathways that result in immune-escape mechanisms. Therefore, the PI3K/AKT pathway is considered an attractive
candidate for therapeutic interventions. We used a modified FATAL assay as an
in-vitro
system to investigate the interaction
between TNBC cell lines and natural killer (NK)-cells. Furthermore we explored the ability of PI3K/AKT inhibition with
AEZS-126 to selectively target TNBC cell proliferation and survival. In parallel we analyzed mechanisms of cytotoxicity
related to PI3K/AKT inhibition. Our results show that TNBC cells (MDA-MB468, HCC1806, HCC1937) can stimulate
the NK-cell immune response significantly stronger than estrogen-receptor (ER)-positive breast cancer cells (MCF-7).
These findings could explain the increased presence of immunosuppressive Tregs infiltrate in human specimens of
TNBC compared to ER-positive breast cancer tissue. AEZS-126 showed good anti-tumor activity in
in-vitro
models of TNBC
as well as in MCF-7 cells. Main mechanism of cytotoxicity seems to be programmed cell death, which could be abrogated
by co-incubation with z-VAD-fmk in MCF-7 and MDA-MB468 cells. In HCC1806 cells, addition of necrostatin-1 has
only slightly protective effects, but in HCC1937 cells, the addition of necrostatin-1 has the same protective effect
as co-incubation with z-VAD-fmk, and this observation argues for cell death caused by apoptosis and necroptosis
in this cell line.
Biography
J C Hahne is currently working for The institute of Cancer Research, Russia. He has several publications in the reputed journals.
hahnejen@yahoo.deJ C Hahne et al., Breast Can Curr Res 2017, 2:4 (Suppl)
DOI: 10.4172/2572-4118-C1-009