title: Effect of PP2A on p34SEI-1 expression in response to ionizing radiation in MCF-7 human breast cancer cells.
abstract: Breast cancer is one of the most common cancers in women and it is highly treatable by radiotherapy and/or radiochemotherapy. A global analysis of the protein expression pattern was performed to identify radiation-responsive proteins in MCF-7 breast cancer cells using 2D-PAGE coupled with MALDI-TOF-MS. When MCF-7 cells were exposed to ionizing radiation (IR) such as γ-rays, eight proteins (GH2, RGS17, BAK1, CCNH, TSG6, RAD51B, IGFBP1, and CASP14) were up-regulated and three proteins (C1QRF, PLSCR2, and p34SE1-1) were down-regulated. In an effort to find what mechanisms are responsible for these changes, we initially focused on p34SE1-1, which is known as a transcriptional regulator and oncogene. Our results show that p34SE1-1 expression is significantly decreased only at the protein level but not at the transcriptional level after IR treatment. We suggest that the B55 regulatory subunit of PP2A, a positive regulator of p34SE1-1, is at least partly responsible for the decreased p34SE1-1 expression, in which the B55 regulatory subunit of PP2A was down-regulated at the protein level as a cellular response to IR. We, therefore, propose that inactivated PP2A resulting from the absence of the B55 subunit may not be able to dephosphorylate p34SE1-1 and therefore increase the phosphory-lated form of p34SE1-1 with low stability. Our further extended study shows that the p34SE1-1 expression level was not changed after H2O2 treatment at either protein or transcriptional levels. This result implies that MCF-7 cells seem to use different signaling pathways in response to IR and H2O2 stresses although both of them belong to the same DNA damage inducing stimuli of reactive oxygen species (ROS).
authors.affiliation: Research Center for Women's Diseases, Division of Biological Sciences, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Samil
authors.initials: S
authors.lastname: Jung
authors.forename: Hyeon-Kyung
authors.initials: HK
authors.lastname: Jeong
authors.forename: Jin
authors.initials: J
authors.lastname: Shin
authors.forename: Myeong-Sok
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D016195:G2 Phase / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D054648:Protein Phosphatase 2 / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors
chemical_list: D009687:Nuclear Proteins; C402464:SERTAD1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D054648:Protein Phosphatase 2