And progression of rheumatoid arthritis. (DOCX)Table S3 Univariate analysis of clinical variables according to time-integrated LDL cholesterol levels. (DOCX) Table S4 Association between patient characteristics and radiographic severity at two years. (DOCX)AcknowledgmentsWe are thankful to Drs. Sungyong You (Departments of Surgery and Biomedical Sciences, Cedars2Sinai Medical Center, Los Angeles, CA) and Namkyo Woo (Department of Statistics, Kyungpook National University, Korea) for helping us with statistical analysis.Author ContributionsConceived and designed the experiments: YJP CSC WUK. Performed the experiments: YJP WUK. Analyzed the data: YJP WUK. Contributed reagents/materials/analysis tools: YJP WUK. Wrote the paper: YJP PE WUK.
Breast cancer is the most common cancer among women with 1.6 million new cases every year worldwide, and it is also the type of cancer with the highest mortality, causing more than 400 000 deaths annually [1]. However, the clinical behavior is diverse and stratification is needed to subgroup patients that benefit from different treatment strategies, including HER2 targeted treatment [2]. Today, prognostication is based on clinical parameters such as lymph node status, tumor size, age and histological grade; complemented by estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor receptor (EGFR/HER2) Title Loaded From File status [3?], which combined separate subgroups with different clinical behavior, including Luminal A, B, HER2 and basal-like tumors [6,7]. However, it is clear that also within subgroups, such as HER2 positive tumors, patients respond differently to selected therapy [8] and that further biological insight is needed. A majorbottleneck in translational research has been the lack of validated antibodies to study novel potentially clinical relevant antigens. We have previously developed antibodies targeting tumorassociated antigens and screened them for differential binding to tumor and normal cells by immunohistochemistry (IHC) [9]. One of the antigens identified as being able to separate normal from malignant cells was the RNA-binding protein T-STAR (testissignal Title Loaded From File transduction and activation of RNA). RNA binding proteins are of major importance as they impact every process in the cell; they may act as splicing and polyadenylation factors, transport and localization factors, stabilizers and destabilizers, modifiers and chaperones [10]. T-STAR is a relatively uncharacterized RNA binding protein belonging to the STAR family, and has important cellular functions such as RNA processing, signal transduction and cell cycle regulation [11,12]. All members share a STAR domain, which is required for RNAbinding and the ability to be modified by several post-translationalT-STAR Protein Expression in Breast Cancermechanisms such as phosphorylation and methylation, which affect the RNA binding capacity [13?7]. A unique feature of these proteins is their capacity to integrate external and internal cell signaling directly to changes in transcription and processing of target RNAs, as they contain both proline rich binding sites for SH3 domains, often found in proteins involved in cell signaling, as well as a RNA binding KH domain [18]. This rapid way of signal transduction has an important role in RNA metabolism [13,16]. T-STAR belongs to the same subgroup as Sam68 and SLM-1, showing 65?0 sequence identity in the STAR domain [16]. Sam68 is by far the most studied member in the STAR family and is more ubiq.And progression of rheumatoid arthritis. (DOCX)Table S3 Univariate analysis of clinical variables according to time-integrated LDL cholesterol levels. (DOCX) Table S4 Association between patient characteristics and radiographic severity at two years. (DOCX)AcknowledgmentsWe are thankful to Drs. Sungyong You (Departments of Surgery and Biomedical Sciences, Cedars2Sinai Medical Center, Los Angeles, CA) and Namkyo Woo (Department of Statistics, Kyungpook National University, Korea) for helping us with statistical analysis.Author ContributionsConceived and designed the experiments: YJP CSC WUK. Performed the experiments: YJP WUK. Analyzed the data: YJP WUK. Contributed reagents/materials/analysis tools: YJP WUK. Wrote the paper: YJP PE WUK.
Breast cancer is the most common cancer among women with 1.6 million new cases every year worldwide, and it is also the type of cancer with the highest mortality, causing more than 400 000 deaths annually [1]. However, the clinical behavior is diverse and stratification is needed to subgroup patients that benefit from different treatment strategies, including HER2 targeted treatment [2]. Today, prognostication is based on clinical parameters such as lymph node status, tumor size, age and histological grade; complemented by estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor receptor (EGFR/HER2) status [3?], which combined separate subgroups with different clinical behavior, including Luminal A, B, HER2 and basal-like tumors [6,7]. However, it is clear that also within subgroups, such as HER2 positive tumors, patients respond differently to selected therapy [8] and that further biological insight is needed. A majorbottleneck in translational research has been the lack of validated antibodies to study novel potentially clinical relevant antigens. We have previously developed antibodies targeting tumorassociated antigens and screened them for differential binding to tumor and normal cells by immunohistochemistry (IHC) [9]. One of the antigens identified as being able to separate normal from malignant cells was the RNA-binding protein T-STAR (testissignal transduction and activation of RNA). RNA binding proteins are of major importance as they impact every process in the cell; they may act as splicing and polyadenylation factors, transport and localization factors, stabilizers and destabilizers, modifiers and chaperones [10]. T-STAR is a relatively uncharacterized RNA binding protein belonging to the STAR family, and has important cellular functions such as RNA processing, signal transduction and cell cycle regulation [11,12]. All members share a STAR domain, which is required for RNAbinding and the ability to be modified by several post-translationalT-STAR Protein Expression in Breast Cancermechanisms such as phosphorylation and methylation, which affect the RNA binding capacity [13?7]. A unique feature of these proteins is their capacity to integrate external and internal cell signaling directly to changes in transcription and processing of target RNAs, as they contain both proline rich binding sites for SH3 domains, often found in proteins involved in cell signaling, as well as a RNA binding KH domain [18]. This rapid way of signal transduction has an important role in RNA metabolism [13,16]. T-STAR belongs to the same subgroup as Sam68 and SLM-1, showing 65?0 sequence identity in the STAR domain [16]. Sam68 is by far the most studied member in the STAR family and is more ubiq.
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