Journal
FRONTIERS IN ONCOLOGY
Volume 4, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2014.00087
Keywords
protein kinase C beta; breast cancer; mammary neoplasms (experimental); tumor microenvironment; stroma; fibroblasts
Categories
Funding
- National Institutes of Health [P01CA09719]
- OSU CCC Pelotonia Postdoctoral Fellowship
- NATIONAL CANCER INSTITUTE [P01CA097189, P30CA016058] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Protein kinase C beta (PKC1) expression in breast cancer is associated with a more aggressive tumor phenotype, yet the mechanism for how PKC1 is pro-tumorigenic in this disease is still unclear. Interestingly, while it is known that PKC1 mediates angiogenesis, immunity, fibroblast function and adipogenesis, all components of the mammary tumor microenvironment (TME), no study to date has investigated whether stromal PKC1 is functionally relevant in breast cancer. Herein, we evaluate mouse mammary tumor virus polyoma middle T-antigen (MMTV PyMT) induced mammary tumorigenesis in the presence and absence of PKC1. We utilize two model systems: one where PKC1 is deleted in both the epithelial and stromal compartments to test the global requirement for PKC1 on tumor formation, and second, where PKC1 is deleted only in the stromal compartment to test its role in the TME. MMTV PyMT mice globally lacking PKC1 live longer and develop smaller tumors with decreased proliferation and decreased macrophage infiltration. Similarly, when PKC1 is null exclusively in the stroma, PyMT-driven B6 cells form smaller tumors with diminished collagen deposition. These experiments reveal for the first time a tumor promoting role for stromal PKC1 in MMTV PyMT tumorigenesis. In corroboration with these results, PKC1 mRNA (Prkcb) is increased in fibroblasts isolated from MMTV PyMT tumors. These data were confirmed in a breast cancer patient cohort. Combined these data suggest the continued investigation of PKC1 in the mammary TME is necessary to elucidate how to effectively target this signaling pathway in breast cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available