Molecular Diagnosis for Breast Cancer

Abstract: Within the past few years a number of genes whose mutated forms are associated with a high risk of breast cancer have been identified, including BRCA1, BRCA2, c-myc, erbB2, and p 53. The identification of these genes, together with rapid advances in techniques for molecular genetic analysis, should improve the diagnosis and therapy of this group of diseases. Allelic losses at other specific loci in breast tumors also may serve as prognostic factors. This article reviews the genetic basis of hereditary and sporadic breast cancers and discusses the clinical application of new molecular knowledge with regard to diagnostic testing, surveillance, and prognostic diagnosis for women with hereditary predispositions or who are at high risk for recurrence of breast cancer. Key words: Breast neoplasms; Oncogenes; Tumor suppressor genes; Loss of heterozygosity product, HER-2 protein. Other highly specific cancer therapies based on results of molecular diagnoses will be available in the near future. In this article we review recent findings, including some from our own research, that have revealed some underlying genetic mechanisms of breast cancer. Familial Breast Cancer A family history of breast cancer has long been recognized as an important risk factor, contributing as it does to about 10% of all breast cancer cases. BRCA1 and BRCA2 have been identified already as tumor suppressor genes associated with familial breast cancer

Scaling the stimulated emission of polarization-entangled photons using passive optical components

Bright sources of polarization-entangled photon pairs are essential components for quantum information technologies. In general, it is necessary to introduce a resonator that combines active optical components such as an electric optical modulator to enhance the stimulated emission of polarization-entangled photons. It is technically difficult to perform the time series operation to output the stimulated entangled photons in the resonator by synchronizing laser pulses. In this paper, we propose a scheme to scale up the stimulated emission of polarization-entangled photon pairs using a resonator with only passive optical components. We show the theoretical aspects of the scheme and also perform a proof-of-principle experimental demonstration of the scheme in a double-pass configuration.Comment: 8 pages, 6 figures, Physical Review A to be publishe

Amelogenin Stimulates Bone Sialoprotein (BSP) Expression Through Fibroblast Growth Factor 2 Response Element and Transforming Growth Factorâ β1 Activation Element in the Promoter of the BSP Gene

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141420/1/jper1482.pd

Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells by Triggering Their Differentiation

SummarySomatic stem cell depletion due to the accumulation of DNA damage has been implicated in the appearance of aging-related phenotypes. Hair graying, a typical sign of aging in mammals, is caused by the incomplete maintenance of melanocyte stem cells (MSCs) with age. Here, we report that irreparable DNA damage, as caused by ionizing radiation, abrogates renewal of MSCs in mice. Surprisingly, the DNA-damage response triggers MSC differentiation into mature melanocytes in the niche, rather than inducing their apoptosis or senescence. The resulting MSC depletion leads to irreversible hair graying. Furthermore, deficiency of Ataxia-telangiectasia mutated (ATM), a central transducer kinase of the DNA-damage response, sensitizes MSCs to ectopic differentiation, demonstrating that the kinase protects MSCs from their premature differentiation by functioning as a “stemness checkpoint” to maintain the stem cell quality and quantity

Regulation of Pancreatic β Cell Mass by Cross-Interaction between CCAAT Enhancer Binding Protein β Induced by Endoplasmic Reticulum Stress and AMP-Activated Protein Kinase Activity

During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to not only insulin resistance but also to pancreatic beta cell failure. Conversely, cell function under various stressed conditions can be restored by reducing ER stress by activating AMP-activated protein kinase (AMPK). However, the details of this mechanism are still obscure. Therefore, the current study aims to elucidate the role of AMPK activity during ER stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-ϐ-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein ϐ (C/EBPϐ) expression levels. The effect of C/EBPϐ phosphorylation on expression levels was also investigated. Vildagliptin and metformin were administered to pancreatic beta cell-specific C/EBPϐ transgenic mice to investigate the relationship between C/EBPϐ expression levels and AMPK activity in the pancreatic islets. When pancreatic beta cells are exposed to ER stress, the accumulation of the transcription factor C/EBPϐ lowers the AMP/ATP ratio, thereby decreasing AMPK activity. In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBPϐ expression. In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBPϐ transgenic mice decreased C/EBPϐ expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity. Enhanced C/EBPϐ expression and decreased AMPK activity act synergistically to induce ER stress-associated pancreatic beta cell failure

Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation.

金沢大学医薬保健研究域　医学系Somatic stem cell depletion due to the accumulation of DNA damage has been implicated in the appearance of aging-related phenotypes. Hair graying, a typical sign of aging in mammals, is caused by the incomplete maintenance of melanocyte stem cells (MSCs) with age. Here, we report that irreparable DNA damage, as caused by ionizing radiation, abrogates renewal of MSCs in mice. Surprisingly, the DNA-damage response triggers MSC differentiation into mature melanocytes in the niche, rather than inducing their apoptosis or senescence. The resulting MSC depletion leads to irreversible hair graying. Furthermore, deficiency of Ataxia-telangiectasia mutated (ATM), a central transducer kinase of the DNA-damage response, sensitizes MSCs to ectopic differentiation, demonstrating that the kinase protects MSCs from their premature differentiation by functioning as a "stemness checkpoint" to maintain the stem cell quality and quantity. © 2009 Elsevier Inc. All rights reserved