title: Effects of the activated mitogen-activated protein kinase pathway via             the c-ros receptor tyrosine kinase on the T47D breast cancer cell line following             alcohol exposure.
abstract: Compared to other cancers affecting women, breast cancer is significantly             associated with alcohol consumption. However, the principles underlying the carcinogenesis             of alcohol-induced breast cancer and the related metastatic mechanisms have yet             to be established. To observe the effect of alcohol on the growth regulation in             breast cancer cells, we identified differentially expressed proteins in alcohol-exposed             human breast cancer T47D cells using gel-based proteomics analysis. The expression             of c-ros receptor tyrosine kinase (ROS1) was increased and activated by autophosphorylation,             thereby activating mitogen- and stress-activated protein kinase 1 (MSK1) through             the mitogen‑activated protein kinase (MAPK) pathway; activated MSK1, in turn,             phosphorylated histone 3 serine 10 (H3S10p) residues in the nucleus. The increase             in H3S10 phosphorylation consequently increased the level of expression of immediate-early             gene such as c-fos. This study demonstrated that when breast cancer cells are             exposed to alcohol, phosphorylated ROS1 activates MSK1 via Erk1/2 in the MAPK             pathway, which then induces modifications to histone residues that regulate gene             expression by 14-3-3 protein recruitment, leading to a lack of control of breast             cancer cell proliferation.
authors.affiliation: Department of Molecular and Life Science, Hanyang University,                     Ansan, Republic of Korea.
authors.forename: Hyung Tae
authors.initials: HT
authors.lastname: Lee
authors.forename: Se Kye
authors.initials: SK
authors.lastname: Kim
authors.forename: Mi Ran
authors.initials: MR
authors.lastname: Choi
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Kyoung Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Young Gyu
authors.initials: YG
authors.lastname: Chai
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D001943:Breast Neoplasms; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D000431:Ethanol / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002070:Butadienes; D017874:Immediate-Early Proteins; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; C113580:U 0126; D000431:Ethanol; C482128:MAP2K2 protein, human; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2