%0 Journal Article
%T Claudin 1 Is Highly Upregulated by PKC in MCF7 Human Breast Cancer Cells and Correlates Positively with PKC¦Å in Patient Biopsies
%A Anne A. Blanchard
%A Arzu Ozturk
%A Carla Penner
%A Etienne Leygue
%A Leigh Murphy
%A Marshall Pitz
%A Nan Wang
%A Sabine Hombach-Klonisch
%A Thomas Klonisch
%A Xiuli Ma
%A Yvonne Myal
%J Archive of "Translational Oncology".
%D 2019
%R 10.1016/j.tranon.2018.12.011
%X Recent studies provide compelling evidence to suggest that the tight junction protein claudin 1, aberrantly expressed in several cancer types, plays an important role in cancer progression. Dysregulation of claudin 1 has been shown to induce epithelial mesenchymal transition (EMT). Furthermore, activation of the ERK signaling pathway by protein kinase C (PKC) was shown to be necessary for EMT induction. Whether PKC is involved in regulating breast cancer progression has not been addressed. The PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA) was used to investigate the effect of PKC activity on claudin 1 transcription and protein levels, subcellular distribution, and alterations in EMT markers in human breast cancer (HBC) cell lines. As well, tissue microarray analysis (TMA) of a large cohort of invasive HBC biopsies was conducted to investigate correlations between claudin 1 and PKC isomers. TPA upregulated claudin 1 levels in all HBC cell lines analyzed. In particular, a high induction of claudin 1 protein was observed in the MCF7 cell line. TPA treatment also led to an accumulation of claudin 1 in the cytoplasm. Additionally, we demonstrated that the upregulation of claudin 1 was through the ERK signaling pathway. In patient biopsies, we identified a significant positive correlation between claudin 1, PKC¦Á, and PKC¦Å in ER+ tumors. A similar correlation between claudin 1 and PKC¦Å was identified in ER£¿ tumors, and high PKC¦Å was associated with shorter disease-free survival. Collectively, these studies demonstrate that claudin 1 and the ERK signaling pathway are important players in HBC progression
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349319/