ATM suppresses c-Myc overexpression in the mammary epithelium in response to estrogen.

ATM gene mutation carriers are predisposed to estrogen-receptor-positive breast cancer (BC). ATM prevents BC oncogenesis by activating p53 in every cell; however, much remains unknown about tissue-specific oncogenesis after ATM loss. Here, we report that ATM controls the early transcriptional response to estrogens.

Supplementation with Fermented Barley Extract Prevents Mammary Epithelial Cell Invasion in an Early Breast Cancer Model.

Diet-based prevention of malignant transformation contributes to the maintenance of quality of life by avoiding a battle against cancer. Invasion is one of the features of malignant breast cancer, and the prevention of invasion may reduce breast cancer malignancy. A recently established early breast cancer model system showed mammary ductal dysplasia with invasion in mice.

A nontoxic fungal natural product modulates fin regeneration in zebrafish larvae upstream of FGF-WNT developmental signaling.

Background: The regeneration of larvae zebrafish fin emerged as a new model of regeneration in the last decade. In contrast to genetic tools to study fin regeneration, chemical probes to modulate and interrogate regeneration processes are not well developed.

Results: We set up a zebrafish larvae fin regeneration assay system and tested activities of natural product compounds and extracts, prepared from various microbes.

Eribulin mesylate-induced c-Fos upregulation enhances cell survival in breast cancer cell lines.

Anticancer agents are used for cancer therapy. Studies on the biological response to treatment with an agent facilitate its effective use. Eribulin mesylate (eribulin) is an anticancer agent.

Estrogen Induces Mammary Ductal Dysplasia via the Upregulation of Myc Expression in a DNA-Repair-Deficient Condition.

Mammary ductal dysplasia is a phenotype observed in precancerous lesions and early-stage breast cancer. However, the mechanism of dysplasia formation remains elusive. Here we show, by establishing a novel dysplasia model system, that estrogen, a female hormone, has the potential to cause mammary ductal dysplasia.

Targeting Phosphorylation of Y-Box-Binding Protein YBX1 by TAS0612 and Everolimus in Overcoming Antiestrogen Resistance.

Nuclear expression of Y-box-binding protein (YBX1) is closely correlated with clinical poor outcomes and drug resistance in breast cancer. Nuclear translocation of YBX1 is facilitated by YBX1 phosphorylation at serine 102 by AKT, p70S6K, and p90RSK, and the phosphorylated YBX1 (pYBX1) promotes expression of genes related to drug resistance and cell growth. A forthcoming problem to be addressed is whether targeting the phosphorylation of YBX1 overcomes antiestrogen resistance by progressive breast cancer.

In silico analysis-based identification of the target residue of integrin α6 for metastasis inhibition of basal-like breast cancer.

Metastasis causes death in breast cancer patients. To inhibit breast cancer metastasis, we focused on integrin α6, a membrane protein that contributes to cell migration and metastasis. According to in silico analysis, we identified Asp-358 as an integrin α6-specific vertebrate-conserved residue and consequently as a potential therapeutic target.

Y-box binding protein YBX1 and its correlated genes as biomarkers for poor outcomes in patients with breast cancer.

The enhanced expression of the Y-box binding protein YBX1 is consistently correlated with poor outcomes or reduced survival of breast cancer patients. However, the mechanism underlying the association between increased YBX1 expression and poor outcomes has yet to be revealed. We searched a database for the top 500 genes that are positively or negatively correlated with YBX1 and with ESR1 in breast cancer patients.

BRCA1 ensures genome integrity by eliminating estrogen-induced pathological topoisomerase II-DNA complexes.

Women having BRCA1 germ-line mutations develop cancer in breast and ovary, estrogen-regulated tissues, with high penetrance. Binding of estrogens to the estrogen receptor (ER) transiently induces DNA double-strand breaks (DSBs) by topoisomerase II (TOP2) and controls gene transcription. TOP2 resolves catenated DNA by transiently generating DSBs, TOP2-cleavage complexes (TOP2ccs), where TOP2 covalently binds to 5' ends of DSBs.

Sal-like 4 protein levels in breast cancer cells are post-translationally down-regulated by tripartite motif-containing 21.

Sal-like 4 (SALL4) is a transcription factor that enhances proliferation and migration in breast cancer cells. SALL4 expression therefore has the potential to promote cancer malignancy. However, the regulatory mechanisms involved in SALL4 protein expression have not been thoroughly elucidated.

5-Chloro-2,4-dihydroxypyridine, CDHP, prevents lung metastasis of basal-like breast cancer cells by reducing nascent adhesion formation.

A drug for metastasis prevention is necessary. The orally administered anticancer drug S-1 contributes to cancer therapy. In a mouse xenograft model of metastatic breast cancer from our previous study, the administration of S-1 inhibited lung metastasis.

SALL4 - KHDRBS3 network enhances stemness by modulating CD44 splicing in basal-like breast cancer.

Understanding the mechanism by which cancer cells enhance stemness facilitates cancer therapies. Here, we revealed that a stem cell transcription factor, SALL4, functions to enhance stemness in basal-like breast cancer cells. We used shRNA-mediated knockdown and gene overexpression systems to analyze gene functions.

The Sal-like 4 - integrin α6β1 network promotes cell migration for metastasis via activation of focal adhesion dynamics in basal-like breast cancer cells.

During metastasis, cancer cell migration is enhanced. However, the mechanisms underlying this process remain elusive. Here, we addressed this issue by functionally analyzing the transcription factor Sal-like 4 (SALL4) in basal-like breast cancer cells.

A homeobox protein, NKX6.1, up-regulates interleukin-6 expression for cell growth in basal-like breast cancer cells.

Among breast cancer subtypes, basal-like breast cancer is particularly aggressive, and research on the molecules involved in its pathology might contribute to therapy. In this study, we found that expression of NKX6.1, a homeobox transcription factor, is higher in basal-like breast cancer than in other subtypes.

Data of a fluorescent imaging-based analysis of anti-cancer drug effects on three-dimensional cultures of breast cancer cells.

Three-dimensional (3D) cell culture is a powerful tool to study cell growth under 3D condition. To perform a simple test for anti-cancer drugs in 3D culture, visualization of non-proliferated cells is required. We propose a fluorescent imaging-based assay to analyze cancer cell proliferation in 3D culture.

An optical labeling-based proliferation assay system reveals the paracrine effect of interleukin-6 in breast cancer.

Proliferation analysis is one of the basic approaches to characterize various cell types. In conventional cell proliferation assays, the same sample cannot be observed over time, nor can a specific group within a heterogeneous population of cells, for example, cancerous cells, be analyzed separately. To overcome these limitations, we established an optical labeling-based proliferation assay system with the Kaede protein, whose fluorescence can be irreversibly photo converted from green to red by irradiation.

Regenerative responses after mild heart injuries for cardiomyocyte proliferation in zebrafish.

Background: The zebrafish heart regenerates after various severe injuries. Common processes of heart regeneration are cardiomyocyte proliferation, activation of epicardial tissue, and neovascularization. In order to further characterize heart regeneration processes, we introduced milder injuries and compared responses to those induced by ventricular apex resection, a widely used injury method.

Sal-like 4 (SALL4) suppresses CDH1 expression and maintains cell dispersion in basal-like breast cancer.

In cell cultures, the dispersed phenotype is indicative of the migratory ability. Here we characterized Sal-like 4 (SALL4) as a dispersion factor in basal-like breast cancer. Our shRNA-mediated SALL4 knockdown system and SALL4 overexpression system revealed that SALL4 suppresses the expression of adhesion gene CDH1, and positively regulates the CDH1 suppressor ZEB1.

Life-long preservation of the regenerative capacity in the fin and heart in zebrafish.

The zebrafish is a widely used model animal to study the regeneration of organs, such as the fin and heart. Their average lifetime is about 3 years, and recent studies have shown that zebrafish exhibit aging-related degeneration, suggesting the possibility that aging might affect regenerative potential. In order to investigate this possibility, we compared regeneration of the fin and heart after experimental amputation in young (6-12 month old) and old (26-36 month old) fish.

Migration of cardiomyocytes is essential for heart regeneration in zebrafish.

Adult zebrafish possess a significant ability to regenerate injured heart tissue through proliferation of pre-existing cardiomyocytes, which contrasts with the inability of mammals to do so after the immediate postnatal period. Zebrafish therefore provide a model system in which to study how an injured heart can be repaired. However, it remains unknown what important processes cardiomyocytes are involved in other than partial de-differentiation and proliferation.

Islet1 regulates establishment of the posterior hindlimb field upstream of the Hand2-Shh morphoregulatory gene network in mouse embryos.

How divergent genetic systems regulate a common pathway during the development of two serial structures, forelimbs and hindlimbs, is not well understood. Specifically, HAND2 has been shown to regulate Shh directly to initiate its expression in the posterior margin of the limb mesenchyme. Although the Hand2-Shh morphoregulatory system operates in both the forelimb and hindlimb bud, a recent analysis suggested that its upstream regulation is different in the forelimb and hindlimb bud.

Islet1-mediated activation of the β-catenin pathway is necessary for hindlimb initiation in mice.

The transcriptional basis of vertebrate limb initiation, which is a well-studied system for the initiation of organogenesis, remains elusive. Specifically, involvement of the β-catenin pathway in limb initiation, as well as its role in hindlimb-specific transcriptional regulation, are under debate. Here, we show that the β-catenin pathway is active in the limb-forming area in mouse embryos.

HMGB factors are required for posterior digit development through integrating signaling pathway activities.

The chromatin factors Hmgb1 and Hmgb2 have critical roles in cellular processes, including transcription and DNA modification. To identify the function of Hmgb genes in embryonic development, we generated double mutants of Hmgb1;Hmgb2 in mice. While double null embryos arrest at E9.

Functional and comparative genomics analyses of pmp22 in medaka fish.

Background: Pmp22, a member of the junction protein family Claudin/EMP/PMP22, plays an important role in myelin formation. Increase of pmp22 transcription causes peripheral neuropathy, Charcot-Marie-Tooth disease type1A (CMT1A). The pathophysiological phenotype of CMT1A is aberrant axonal myelination which induces a reduction in nerve conduction velocity (NCV).

Molecular mechanism of transcriptional cascade initiated by the EvgS/EvgA system in Escherichia coli K-12.

Using an EvgS-active mutant (evgS1) in combination with gene deletions, we clarified the molecular mechanism of the transcriptional cascade of acid resistance and multidrug resistance genes initiated by the EvgS/EvgA two-component system in Escherichia coli, followed by sequential induction of the transcriptional regulators, YdeO and GadE. Overexpression of EvgA, the response regulator of the EvgS/EvgA system, is known to induce the expression of a number of acid resistance and multidrug resistance genes, in which the EvgA-YdeO-GadE circuit is involved, but the role of the sensor EvgS in this circuit has remained unsolved. Our results suggest that the transcriptional cascade initiated by the EvgS/EvgA system in fact functions for acid and drug resistance in E.