alternate estrogen receptors promote invasion of inflammatory breast cancer cells via non-genomic signaling替代雌激素受体通过non-genomic促进炎性乳腺癌细胞的入侵信号.pdfVIP

Alternate Estrogen Receptors Promote Invasion of Inflammatory Breast Cancer Cells via Non-Genomic Signaling 1 2 3 1 Kazufumi Ohshiro , Arnold M. Schwartz , Paul H. Levine , Rakesh Kumar * 1 Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, D.C., United States of America, 2 Department of Pathology, The George Washington University Medical Center, Washington, D.C., United States of America, 3 Department of Epidemiology and Biostatistics, The George Washington University Medical Center, Washington, D.C., United States of America Abstract Although Inflammatory Breast Cancer (IBC) is a rare and an aggressive type of locally advanced breast cancer with a generally worst prognosis, little work has been done in identifying the status of non-genomic signaling in the invasiveness of IBC. The present study was performed to explore the status of non-genomic signaling as affected by various estrogenic and anti-estrogenic agents in IBC cell lines SUM149 and SUM190. We have identified the presence of estrogen receptor a (ERa) variant, ERa36 in SUM149 and SUM190 cells. This variant as well as ERb was present in a substantial concentration in IBC cells. The treatment with estradiol (E2), anti-estrogenic agents 4-hydroxytamoxifen and ICI 182780, ERb specific ligand DPN and GPR30 agonist G1 led to a rapid activation of p-ERK1/2, suggesting the involvement of ERa36, ERb and GPR30 in the non-genomic signaling pathway in these cells. We also found a substantial increase in the cell migration and invasiveness of SUM149 cells upon the treatment with these ligands. Both basal and ligand-induced migration and invasiveness of SUM149 cells were