SOMATIC CELL HYBRIDS BETWEEN MOUSE PERITONEAL MACROPHAGES AND SV40-TRANSFORMED HUMAN CELLS : I. Positive Control of the Transformed Phenotype by the Human Chromosome 7 Carrying the SV40 Genome

Fusion of mouse peritoneal macrophages with SV40-transformed human cells, deficient in hypoxanthine guanine phosphoribosyltransferase, resulted in the formation of transformed somatic cell hybrids which contained, without exception, the human chromosome 7 carrying the SV40 genome. It is postulated that the hybridization of mouse nondividing cells with human cancer cells could permit the identification of the human "oncogenic" chromosome(s) present in human cancer cells, since such chromosome(s) should be retained by the totality of the mouse-human hybrid cells

Fez1/Lzts1 a new mitotic regulator implicated in cancer development

Considerable evidence has accumulated suggesting that cancer has genetic origin, based on the development of genomic alterations, such as deletions, mutations, and/or methylations in critical genes for homeostasis of cellular functions, including cell survival, DNA replication and cell cycle control. Mechanism controlling the precise timing and sequence of cell cycle events as well as checkpoints insuring fidelity of those events are key targets that when disrupted could result in tumorigenesis. Mitosis is the process by which a cell duplicates its genetic information (DNA), in order to generate two, identical, daughter cells. In addition each daughter cell must receive one centrosome and the appropriate complements of cytoplasm and organelles. This process is conventionally divided in to five distinct stages: prophase, prometaphase, metaphase, anaphase and telophase that correspond to a different morphology of the cell. The entry into mitosis (M) is under the control of the cyclin dependent kinase Cdk1. During G2, the kinases Wee1 and Myt1 phosphorylate Cdk1 at T14/Y15 residues, rendering it inactive. The transition from G2 to M is promoted by the activation of Cdk1 via dephosphorylation by the Cdk1 phosphatase Cdc25C. Activated Cdk1 complexes translocate into the nucleus during prophase where phosphorylate numerous substrates in order to enhance their activation as the cells progresses trough prophase, prometaphase, and metaphase

Micro-RNA Expression and Function in Lymphomas

The recent discovery of microRNAs (miRNAs) has introduced a new layer of complexity to the process of gene regulation. MiRNAs are essential for cellular function, and their dysregulation often results in disease. Study of miRNA expression and function in animal models and human lymphomas has improved our knowledge of the pathogenesis of this heterogeneous disease. In this paper, we attempt to describe the expression of miRNAs and their function in lymphomas and discuss potential miRNA-based therapies in the diagnosis and treatment of lymphomas

Upregulation of long noncoding RNA MIAT in aggressive form of chronic lymphocytic leukemias.

Long noncoding RNAs (lncRNAs) are non-proten-coding transcripts of more than 200 nucleotides generated by RNA polymerase II and their expressions are tightly regulated in cell type specific- and/or cellular differential stage specific- manner. MIAT, originally isolated as a candidate gene for myocardial infarction, encodes lncRNA (termed MIAT). Here, we determined the expression level of MIAT in established leukemia/lymphoma cell lines and found its upregulation in lymphoid but not in myeloid cell lineage with mature B cell phenotype. MIAT expression level was further determined in chronic lymphocytic leukemias (CLL), characterized by expansion of leukemic cells with mature B phenotype, to demonstrate relatively high occurrence of MIAT upregulation in aggressive form of CLL carrying either 17p-deletion, 11q-deletion, or Trisomy 12 over indolent form carrying 13p-deletion. Furthermore, we show that MIAT constitutes a regulatory loop with OCT4 in malignant mature B cell, as was previously reported in mouse pulripotent stem cell, and that both molecules are essential for cell survival

MicroRNAs in melanoma development and resistance to target therapy

microRNAs constitute a complex class of pleiotropic post-transcriptional regulators of gene expression involved in the control of several physiologic and pathologic processes. Their mechanism of action is primarily based on the imperfect matching of a seed region located at the 5' end of a 21-23 nt sequence with a partially complementary sequence located in the 3' untranslated region of target mRNAs. This leads to inhibition of mRNA translation and eventually to its degradation. Individual miRNAs are capable of binding to several mRNAs and several miRNAs are capable of influencing the function of the same mRNAs. In recent years networks of miRNAs are emerging as capable of controlling key signaling pathways responsible for the growth and propagation of cancer cells. Furthermore several examples have been provided which highlight the involvement of miRNAs in the development of resistance to targeted drug therapies. In this review we provide an updated overview of the role of miRNAs in the development of melanoma and the identification of the main downstream pathways controlled by these miRNAs. Furthermore we discuss a group of miRNAs capable to influence through their respective up- or down-modulation the development of resistance to BRAF and MEK inhibitors