BBB seminar: Bjørn Steen Skålhegg
Ablation of PKA-Cβ2 subunit in mice curtails progression of breast adenocarcinoma and turns "cold" tumor "hot"
Bjørn Steen Skålhegg
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo
Protein kinase A (PKA) is a member of the serine-threonine kinase superfamily that transduces cAMP signals through the catalytic subunits Cα and Cβ. Several studies highlighted the role of PKA in promoting progression and aggression of breast cancer; however, its contribution to cancer immune editing remains unexplored. The splice variant Cβ2 is exclusively expressed in immune cells and mediates an anti-proliferative effect by phosphorylation of the C-terminal Src kinase (CsK). To determine the role of PKA-Cβ2 in regulating cancer progression, eight to twelve weeks old, Cβ2 knockout and wild type mice were injected with estrogen receptor (ER+) EO771 adenocarcinoma cells and tumor growth was assessed. This showed a delay in tumor growth in Cβ2 KO mice associated with elevated infiltration of CD8 + and CD4+ T lymphocytes in their primary tumors as compared with wild type counterparts. Moreover, flow cytometric analysis of spleen cells revealed increased numbers of circulating CD4+ Th1, Th9 and Th17 in Cβ2 KO mice. In addition, predicted quantification of immune cell types in peripheral blood mononuclear cells (PBMC) and biopsies from human breast cancer patients revealed that differential expression of Cβ2 correlated with circulating and tumor infiltrating immune cell types. We suggest that our findings will lead to a better understanding of the role of Cβ2 in modulating immune responses against tumor cells and may identify Cβ2 as a target for cancer immunotherapy.
Chairperson: Linda Elin Birkhaug Stuhr, Department of Biomedicine