Medicine and Health Sciences Commons^™

Mir-29 Regulates Mcl-1 Protein Expression And Apoptosis., Justin L. Mott, Shogo Kobayashi, Steven F. Bronk, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

Cellular expression of Mcl-1, an anti-apoptotic Bcl-2 family member, is tightly regulated. Recently, Bcl-2 expression was shown to be regulated by microRNAs, small endogenous RNA molecules that regulate protein expression through sequence-specific interaction with messenger RNA. By analogy, we reasoned that Mcl-1 expression may also be regulated by microRNAs. We chose human immortalized, but non-malignant, H69 cholangiocyte and malignant KMCH cholangiocarcinoma cell lines for these studies, because Mcl-1 is dysregulated in cells with the malignant phenotype. By in silico analysis, we identified a putative target site in the Mcl-1 mRNA for the mir-29 family, and found that mir-29b was highly …

The Notch Regulator Maml1 Interacts With P53 And Functions As A Coactivator., Yongtong Zhao, Rebecca B. Katzman, Laurie M. Delmolino, Ishfaq Bhat, Ying Zhang, Channabasavaiah B. Gurumurthy, Aleksandra Germaniuk-Kurowska, Honey V. Reddi, Aharon Solomon, Mu-Sheng Zeng, Aisha Kung, Hui Ma, Qingshen Gao, Goberdhan Dimri, Adina Stanculescu, Lucio Miele, Lizi Wu, James D. Griffin, David E. Wazer, Hamid Band, Vimla Band

Journal Articles: Biochemistry & Molecular Biology

Members of the evolutionarily conserved Mastermind (MAM) protein family, including the three related mammalian Mastermind-like (MAML) proteins MAML1-3, function as crucial coactivators of Notch-mediated transcriptional activation. Given the recent evidence of cross-talk between the p53 and Notch signal transduction pathways, we have investigated whether MAML1 may also be a transcriptional coactivator of p53. Indeed, we show here that MAML1 is able to interact with p53. We show that MAML1-p53 interaction involves the N-terminal region of MAML1 and the DNA-binding domain of p53, and we use a chromatin immunoprecipitation assay to show that MAML1 is part of the activator complex that …

Colon Carcinoma Cells Harboring Pik3ca Mutations Display Resistance To Growth Factor Deprivation Induced Apoptosis., J. Wang, Karen Kuropatwinski, Jennie Hauser, Michael R. Rossi, Yunfei Zhou, Alexis Conway, Julie L.C. Kan, Neil W. Gibson, James K.V. Willson, John K. Cowell, Michael G. Brattain

Journal Articles: Eppley Institute

PIK3CA, encoding the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), is mutated in a variety of human cancers. We screened the colon cancer cell lines previously established in our laboratory for PIK3CA mutations and found that four of them harbored gain of function mutations. We have now compared a panel of mutant and wild-type cell lines for cell proliferation and survival in response to stress. There was little difference in PI3K activity between mutant PIK3CA-bearing cells (mutant cells) and wild-type PIK3CA-bearing cells (wild-type cells) under optimal growth conditions. However, the mutant cells showed constitutive PI3K activity during growth factor deprivation …

Sustained Il-6/Stat-3 Signaling In Cholangiocarcinoma Cells Due To Socs-3 Epigenetic Silencing., Hajime Isomoto, Justin L. Mott, Shogo Kobayashi, Nathan W. Werneburg, Steve F. Bronk, Serge Haan, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND & AIMS: Interleukin 6 (IL-6)-mediated signal transducers and activators of transcription 3 (STAT-3) phosphorylation (activation) is aberrantly sustained in cholangiocarcinoma cells resulting in enhanced myeloid cell leukemia 1 (Mcl-1) expression and resistance to apoptosis. Because suppressor of cytokine signaling 3 (SOCS) controls the IL-6/STAT-3 signaling pathway by a classic feedback loop, the aims of this study were to examine SOCS-3 regulation in human cholangiocarcinoma.

METHODS: SOCS-3 expression was assessed in human cholangiocarcinoma tissue and the Mz-ChA-1 and CCLP1 human cholangiocarcinoma cell lines.

RESULTS: An inverse correlation was observed between phospho-STAT-3 and SOCS-3 protein expression in cholangiocarcinoma. In those cancers …