Research Papers:
T-helper 1-type cytokines induce apoptosis and loss of HER-family oncodriver expression in murine and human breast cancer cells
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Abstract
Prachi Namjoshi1, Lori Showalter1, Brian J. Czerniecki2 and Gary K. Koski1
1 Department of Biological Sciences, Kent State University, Kent, Ohio, USA
2 Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Correspondence to:
Gary K. Koski, | email: | dendritic_cell@hotmail.com |
Keywords: apoptosis; HER-2; T-helper 1; IFN-γ; TNF-α
Received: February 16, 2016 Accepted: May 12, 2016 Published: October 15, 2019
ABSTRACT
A recent neoadjuvant vaccine trial for early breast cancer induced strong Th1 immunity against the HER-2 oncodriver, complete pathologic responses in 18% of subjects, and for many individuals, dramatically reduced HER-2 expression on residual disease. To explain these observations, we investigated actions of Th1 cytokines (TNF-α and IFN-γ) on murine and human breast cancer cell lines that varied in the surface expression of HER-family receptor tyrosine kinases. Breast cancer lines were broadly sensitive to the combination of IFN-γ and TNF-α, as evidenced by lower metabolic activity, lower proliferation, and enhanced apoptosis, and in some cases a reversible inhibition of surface expression of HER proteins. Apoptosis was accompanied by caspase-3 activation. Furthermore, the pharmacologic caspase-3 activator PAC-1 mimicked both the killing effects and HER-2-suppressive activities of Th1 cytokines, while a caspase 3/7 inhibitor could prevent cytokine-induced HER-2 loss. These studies demonstrate that many
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PII: 10298