nuclear entry of activated mapk is restricted in primary ovarian and mammary epithelial cells核的激活mapk是主要限制在卵巢和乳腺上皮细胞.pdfVIP

Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells 1,2 3 3 1,2 3 Elizabeth R. Smith *, Kathy Qi Cai , Jennifer L. Smedberg , Melina M. Ribeiro , Malgorzata E. Rula , 3 3 1,2 Carolyn Slater , Andrew K. Godwin , Xiang-Xi Xu 1 Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America, 2 Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, United States of America, 3 Ovarian Cancer and Tumor Cell Biology Programs, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America Abstract Background: The MAPK/ERK1/2 serine kinases are primary mediators of the Ras mitogenic signaling pathway. Phosphorylation by MEK activates MAPK/ERK in the cytoplasm, and phospho-ERK is thought to enter the nucleus readily to modulate transcription. Principal Findings: Here, however, we observe that in primary cultures of breast and ovarian epithelial cells, phosphorylation and activation of ERK1/2 are disassociated from nuclear translocalization and transcription of downstream targets, such as c-Fos, suggesting that nuclear translocation is limited in primary cells. Accordingly, in import assays in vitro, primary cells showed a lower import activity for ERK1/2 than cancer cells, in which activated MAPK readily translocated into the nucleus and activated c-Fos expression. Primary cells express lower levels of nuclear pore complex proteins and the nuclear transport factors, impor