S should be performed to clarify the influences of these two novel adipokines, progranulin and CTRP3, on the pathogenesis and outcomes of chronic metabolic disorders and cardiovascular disease.Supporting InformationTable S1 Multiple Stepwise Regression Analyses for Determinant Factors Associated with Serum Progranulin and CTRP3 Levels. (DOC)Author ContributionsConceived and designed the experiments: HJY BSY KMC. Performed the experiments: HCH HYC SJY. Analyzed the data: SYH. Contributed reagents/materials/analysis tools: DSC SHB. Wrote the paper: HJY KMC MB.
The molecular changes that occur during breast cancer progression, which include the amplification/overexpression of transcription factors, can disrupt the delicate Dipraglurant balance between cell proliferation, differentiation and apoptosis. C/EBPb is one of those transcription factors, which has been implicated in cell cycle regulation, playing an important role in mammary gland development and oncogene-induced breast tumorigenesis [1?]. Encoded by an intronless gene, C/EBPb is expressed as distinct protein isoforms, which can accomplish distinct biological and regulatory functions, ultimately leading to gene transactivation [5]. The longer C/EBPb proteins (liver-enriched transcriptional activating proteins, LAP1 and LAP2) regulate proliferation and differentiation of many cell types [6]; the shorter protein product (liver-enriched transcriptional inhibitory protein, LIP) lacks the transactivation domain and acts mainly as a dominant-negative [7]. AS LAP isoforms, LIP also binds to the Dorsomorphin (dihydrochloride) consensus sequences within genomic DNA, sometimes even with a higher affinity than the other C/EBPb isoforms [6,7]. In fact, LIP inhibits thetranscriptional activity of LAPs by competing for the same consensus binding sites or by forming inactive heterodimers with them. However, some emerging evidence suggest that LIP can also act as a transcriptional activator in some cellular contexts [5]. In breast, C/EBPb most likely contributes to tumorigenesis through significant elevations in the LIP:LAP ratio, mostly observed in ER-negative, highly proliferative and metastatic mammary tumours, usually associated with a poor patient prognosis [8]. Indeed, LIP isoform overexpression has been associated to a lack of contact inhibition, resulting in proliferation and foci formation in epithelial breast cancer cell lines [9]. It has been hypothesized that aberrant expression of C/EBPb-LIP isoform may contribute to an increased growth rate and result in a more proliferative and aggressive breast carcinoma. P-cadherin, a classical cadherin encoded by the CDH3 gene [10], has been explored by our group for several years and has been also extensively associated with breast tumour aggressiveness. This protein was found to be aberrantly expressed in 20?0 of invasive ductal carcinomas, being strongly associated with proliferative lesions of high histological grade, decreased cellC/EBPb Targets CDH3 Gene in Breast Cancer Cellspolarity and poor patient survival [11?6]. At the in vitro level, we demonstrated that P-cadherin overexpression induces invasion [14], motility and migration of wild-type E-cadherin expressing breast cancer cells, through the secretion of pro-invasive factors, such as matrix metalloproteinase (MMP)-1 and MMP-2 [17]. In fact, P-cadherin-associated functions in breast cancer have been widely studied, which reflects the growing importance of this cadherin in human breast cancer biology and prognosis. However, the.S should be performed to clarify the influences of these two novel adipokines, progranulin and CTRP3, on the pathogenesis and outcomes of chronic metabolic disorders and cardiovascular disease.Supporting InformationTable S1 Multiple Stepwise Regression Analyses for Determinant Factors Associated with Serum Progranulin and CTRP3 Levels. (DOC)Author ContributionsConceived and designed the experiments: HJY BSY KMC. Performed the experiments: HCH HYC SJY. Analyzed the data: SYH. Contributed reagents/materials/analysis tools: DSC SHB. Wrote the paper: HJY KMC MB.
The molecular changes that occur during breast cancer progression, which include the amplification/overexpression of transcription factors, can disrupt the delicate balance between cell proliferation, differentiation and apoptosis. C/EBPb is one of those transcription factors, which has been implicated in cell cycle regulation, playing an important role in mammary gland development and oncogene-induced breast tumorigenesis [1?]. Encoded by an intronless gene, C/EBPb is expressed as distinct protein isoforms, which can accomplish distinct biological and regulatory functions, ultimately leading to gene transactivation [5]. The longer C/EBPb proteins (liver-enriched transcriptional activating proteins, LAP1 and LAP2) regulate proliferation and differentiation of many cell types [6]; the shorter protein product (liver-enriched transcriptional inhibitory protein, LIP) lacks the transactivation domain and acts mainly as a dominant-negative [7]. AS LAP isoforms, LIP also binds to the consensus sequences within genomic DNA, sometimes even with a higher affinity than the other C/EBPb isoforms [6,7]. In fact, LIP inhibits thetranscriptional activity of LAPs by competing for the same consensus binding sites or by forming inactive heterodimers with them. However, some emerging evidence suggest that LIP can also act as a transcriptional activator in some cellular contexts [5]. In breast, C/EBPb most likely contributes to tumorigenesis through significant elevations in the LIP:LAP ratio, mostly observed in ER-negative, highly proliferative and metastatic mammary tumours, usually associated with a poor patient prognosis [8]. Indeed, LIP isoform overexpression has been associated to a lack of contact inhibition, resulting in proliferation and foci formation in epithelial breast cancer cell lines [9]. It has been hypothesized that aberrant expression of C/EBPb-LIP isoform may contribute to an increased growth rate and result in a more proliferative and aggressive breast carcinoma. P-cadherin, a classical cadherin encoded by the CDH3 gene [10], has been explored by our group for several years and has been also extensively associated with breast tumour aggressiveness. This protein was found to be aberrantly expressed in 20?0 of invasive ductal carcinomas, being strongly associated with proliferative lesions of high histological grade, decreased cellC/EBPb Targets CDH3 Gene in Breast Cancer Cellspolarity and poor patient survival [11?6]. At the in vitro level, we demonstrated that P-cadherin overexpression induces invasion [14], motility and migration of wild-type E-cadherin expressing breast cancer cells, through the secretion of pro-invasive factors, such as matrix metalloproteinase (MMP)-1 and MMP-2 [17]. In fact, P-cadherin-associated functions in breast cancer have been widely studied, which reflects the growing importance of this cadherin in human breast cancer biology and prognosis. However, the.
