Occurrence of senescence-escaping cells in doxorubicin-induced senescence is enhanced by PD0332991, a cyclin-dependent kinase 4/6 inhibitor, in colon cancer HCT116 cells.

Cancer treatment induces cellular senescence, and it is considered to be one of the factors that determines treatment outcome. Senescence can be efficiently induced in cultured cells by DNA-damaging drugs, including doxorubicin (DOX), cisplatin and etoposide. Cells in senescence cease proliferation; however, it has been demonstrated that colonies that are formed from cells escaping senescence appear in drug-induced senescence; however, the conditions influencing the emergence of such senescence-escaping cells (SECs) remain unclear.

A novel mechanism of EML4-ALK rearrangement mediated by chromothripsis in a patient-derived cell line.

Introduction: EML4-ALK is a driver oncogene in non-small-cell lung cancer (NSCLC) and has been developed into a promising molecular target for antitumor agents. Although EML4-ALK is reported to be formed by inversion of chromosome 2, other mechanisms of this gene fusion remain unknown. This study aimed to examine the mechanism of EML4-ALK rearrangement using a novel cell line with the EML4-ALK fusion gene.

Chromosome-specific segmentation revealed by structural analysis of individually isolated chromosomes.

Analysis of structural rearrangements at the individual chromosomal level is still technologically challenging. Here we optimized a chromosome isolation method using fluorescent marker-assisted laser-capture and laser-beam microdissection and applied it to structural analysis of two aberrant chromosomes found in a lung cancer cell line. A high-density array-comparative genomic hybridization (array-CGH) analysis of DNA samples prepared from each of the chromosomes revealed that these two chromosomes contained 296 and 263 segments, respectively, ranging from 1.

Amplification of the ABCB1 region accompanied by a short sequence of 200bp from chromosome 2 in lung cancer cells.

Lung cancer sublines No15-80-1 and No15-80-6 were selected by treatment of cell line NCI-H460 with paclitaxel at stepwise increasing concentrations from 50 nmol/L to 800 nmol/L. The two sublines exhibited amplifications of the ABCB1 region (previously MDR1) with different copy number profiles, but shared a common amplification pattern, which has been observed in amplification mediated by the breakage-fusion-bridge (BFB) cycle. Sequence analysis of the distal ends of the amplified regions, which were probably generated in a break-and-fusion of the initial round of the BFB cycle, revealed a head-to-head fused sequence of chromosome 7.

PrognoScan: a new database for meta-analysis of the prognostic value of genes.

Background: In cancer research, the association between a gene and clinical outcome suggests the underlying etiology of the disease and consequently can motivate further studies. The recent availability of published cancer microarray datasets with clinical annotation provides the opportunity for linking gene expression to prognosis. However, the data are not easy to access and analyze without an effective analysis platform.

A signature-based method for indexing cell cycle phase distribution from microarray profiles.

Background: The cell cycle machinery interprets oncogenic signals and reflects the biology of cancers. To date, various methods for cell cycle phase estimation such as mitotic index, S phase fraction, and immunohistochemistry have provided valuable information on cancers (e.g.

17Beta-hydroxysteroid dehydrogenase type 12 in human breast carcinoma: a prognostic factor via potential regulation of fatty acid synthesis.

17beta-Hydroxysteroid dehydrogenase type 12 (17beta-HSD12) has been shown to be involved in elongation of very long chain fatty acid (VLCFA) as well as in biosynthesis of estradiol (E2). 17beta-HSD12 expression was also reported in breast carcinomas but its functions have remained unknown. In this study, we examined the correlation between mRNA expression profiles determined by microarray analysis and tissue E2 concentrations obtained from 16 postmenopausal breast carcinoma cases.

Comparison of murine gene expression profiles between spontaneous and radiation-induced myelogenous leukemias: stochastic and probabilistic expression variances in the former vs radiation-specific expression commonalities in the latter.

Objective: To elucidate the common characteristics of murine radiation-induced myelogenous leukemias, global gene-chip expression profiles were compared with age-matched steady-state bone marrow tissue profiles and spontaneous myelogenous leukemia profiles.

Materials And Methods: Six each of C3H/He mice-derived radiation-induced and spontaneously developed myelogenous leukemias were analyzed. Bone marrow cells from five each of 2- and 21-month-old mice were used to subtract nonleukemic information in the analysis.

The complicated copy number alterations in chromosome 7 of a lung cancer cell line is explained by a model based on repeated breakage-fusion-bridge cycles.

The drug-resistant lung cancer cell line PTX250, which has been previously established by exposure to an anti-cancer drug paclitaxel, has an increased copy number in the MDR1/ABCB1 locus region. In addition, the flanking regions also exhibit aberrant copy numbers, making the copy number profile of chromosome 7 complicated. In this study, we tested whether the breakage-fusion-bridge (BFB) cycle model can explain such copy number alterations.

The MDR1/ABCB1 regional amplification in large inverted repeats with asymmetric sequences and microhomologies at the junction sites.

A multidrug-resistant lung cancer cell line PTX250, established by treatment with the anti-cancer drug paclitaxel, has been demonstrated to have an increased copy number in the 7q21.12 region including the MDR1/ABCB1 gene. The amplicon is 2.

Aromatase localization in human breast cancer tissues: possible interactions between intratumoral stromal and parenchymal cells.

Aromatase is a key enzyme in intratumoral estrogen production required for the production of estrogens through the conversion of serum androgens in postmenopausal breast cancer patients. There have been, however, controversies regarding the intratumoral localization of aromatase in human breast carcinoma tissues. Therefore, we have first examined the intratumoral localization of aromatase mRNA/protein in 19 breast carcinomas using laser capture microdissection/quantitative reverse transcription-PCR (RT-PCR) and immunohistochemistry.

Gene amplification and expression in lung cancer cells with acquired paclitaxel resistance.

A paclitaxel-resistant subline was generated from the non-small lung cancer cell line NCI-H460 by stepwise selection in paclitaxel from 0.032 to 250 nmol/L. The resulting subline, designated NCI-H460/PTX250, showed 792-fold resistance against paclitaxel compared with the parental cell line NCI-H460.

Immunolocalization of liver receptor homologue-1 (LRH-1) in human breast carcinoma: possible regulator of insitu steroidogenesis.

Liver receptor homologue-1 (LRH-1) belongs to a class of nuclear orphan receptor. We examined immunolocalization of LRH-1 in 106 breast carcinomas. LRH-1 immunoreactivity was detected in 43% of the invasive ductal carcinoma.

Expression of the steroid and xenobiotic receptor and its possible target gene, organic anion transporting polypeptide-A, in human breast carcinoma.

Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR) has been shown to play an important role in the regulation of genes related to xenobiotic detoxification, such as cytochrome P450 3A4 and multidrug resistance gene 1. Cytochrome P450 enzymes, conjugation enzymes, and transporters are all considered to be involved in the resistance of breast carcinoma to chemotherapeutic or endocrine agents. However, the expression of SXR/hPXR proteins and that of its target genes and their biological or clinical significance have not been examined in human breast carcinomas.

Genes commonly upregulated by hypoxia in human breast cancer cells MCF-7 and MDA-MB-231.

Hypoxia is a stress that causes alterations in signal transduction and gene instability. In the cancer microenvironment, hypoxia plays a significant role in forming a tumor phenotype and tumor progression. We aimed to identify the genes upregulated by hypoxia in human breast cancer cell lines, a hormone-dependent MCF-7 and a hormone-independent MDA-MB-231, using microarray analysis.

Mechanisms of benzene-induced hematotoxicity and leukemogenicity: cDNA microarray analyses using mouse bone marrow tissue.

Although the mechanisms underlying benzene-induced toxicity and leukemogenicity are not yet fully understood, they are likely to be complicated by various pathways, including those of metabolism, growth factor regulation, oxidative stress, DNA damage, cell cycle regulation, and programmed cell death. With this as a background, we performed cDNA microarray analyses on mouse bone marrow tissue during and after a 2-week benzene exposure by inhalation. Our goal was to clarify the mechanisms underlying the hematotoxicity and leukemogenicity induced by benzene at the level of altered multigene expression.

The localization change of Ybr078w/Ecm33, a yeast GPI-associated protein, from the plasma membrane to the cell wall, affecting the cellular function.

The YBR078W/ECM33 gene of Saccharomyces cerevisiae encodes a glycosylphosphatidylinositol (GPI)-attached protein and its disruptant strain exhibited a temperature-sensitive (ts) growth defect. A HA-tagged Ybr078w protein, which complemented the ts growth phenotype of the ybr078wdelta strain, was predominantly located on the plasma membrane by GPI anchoring. To examine the requirement of the GPI anchoring on the plasma membrane for the function, the omega-minus region of Ybr078w was replaced with those of Ydr534c/Fit1 and Ynl327w/Egt2, which are known as GPI-dependent cell wall proteins.

Mapping of early firing origins on a replication profile of budding yeast.

Background: Understanding of the firing time determination of replication origins in the entire genome will require a genome-wide survey of replication origins and their mapping on chromosomes. A microarray technology was applied to obtain a genome-wide profile of DNA replication and to classify early firing origins.

Results: A total of 260 potential replication origins (PROs) were identified in the entire budding yeast genome: 247 as defined peaks on the replication profile and 13 as regions located in the chromosomal termini.

Sequence-based approach for identification of cell wall proteins in Saccharomyces cerevisiae.

Open reading frames (ORFs) in the genome of Saccharomyces cerevisiae were screened for cell wall proteins and extracellular proteins, using an in silico sequence analysis combined with biochemical examination. The selection criteria used in the sequence analysis were the presence of a signal sequence for secretion and the absence of any targeting and retention signal to/in intracellular components. By using the PSORT II program, 163 ORFs/proteins were selected as potential extracellular proteins, including cell wall proteins.

A controllable gene-expression system for the pathogenic fungus Candida glabrata.

A system for controlling gene expression was established in the pathogenic fungus Candida glabrata to elucidate the physiological functions of genes. To control the expression of the gene of interest, the C. glabrata cells were first transformed with the plasmid carrying the tetracycline repressor-transactivator fusion tetR::GAL4, then with the DNA fragment containing the controllable cassette, the tetracycline operator chimeric promoter (tetO::ScHOP1).