Bone mineral contains hydroxyapatite (HA). This is the surface that mature osteoblasts and osteocytes interact with. Synthetic HA is widely used in orthopedic surgeries as an implant or implant coating. The bone-like HA surfaces increase implant union and bone formation; however, the mechanisms accounting for this effect on osteoblasts are not known. In this study, we compared gene expression profiles of osteoblasts responding to HA or plastic surfaces for 24 h. Expression profiles were also compared between HA discs processed with gravity-sieved compared with combined gravity and air-jet-sieved HA powders. The latter, composed of smaller HA particles, exhibits an increase in grain boundary surface area. Discs made with either HA powder similarly up-regulated osteoblast expression of 10 genes (including proliferin 3, Glvr-1, DMP-1, and tenascin C) and down-regulated 15 genes (such as osteoglycin) by more than 2-fold compared with plastic surfaces. The overall changes are indicative of an immediate (24-h) response to the HA surface and a trend toward osteoblast differentiation. In addition, subsets of modulated genes exist that are unique to each HA subtype. Taken together, we identified HA responsive genes evident within 24 h of surface contact, indicating a critical role for extracellular mineral surfaces in the regulation of osteoblast gene expression and phenotype.
Both estrogen (E) and progesterone (P) are implicated in the etiology of human breast cancer. Defining their mechanisms of action, particularly in vivo, is relevant to the prevention and therapy of breast cancer. We investigated the molecular and cellular mechanisms of E and/or P-induced in vivo proliferation, in the normal rat mammary gland and in hormone-dependent rat mammary cancers which share many characteristics with the normal human breast and hormone-dependent breast cancers. We show that E+P treatment induced significantly greater proliferation in both the normal gland and mammary cancers compared to E alone. In both the normal gland and tumors, E+P-induced proliferation was mediated through the increased production of amphiregulin (Areg), an epidermal growth factor receptor (EGFR) ligand, and the activation of intracellular signaling pathways (Erk, Akt, JNK) downstream of EGFR that regulate proliferation. In vitro experiments using rat primary mammary organoids or T47D breast cancer cells confirmed that Areg and the synthetic progestin, R5020, synergize to promote cell proliferation through EGFR signaling. Iressa, an EGFR inhibitor, effectively blocked this proliferation. These results indicate that mediators of cross talk between E, P, and EGFR pathways may be considered as relevant molecular targets for the therapy of hormone-dependent breast cancers, especially in premenopausal women.Electronic supplementary materialThe online version of this article (doi:10.1007/s12672-010-0048-0) contains supplementary material, which is available to authorized users.
The risks and benefits of diets and supplements containing the estrogenic soy isoflavone genistein are not well established. We report that 10 nm genistein potently induces the granzyme B inhibitor, proteinase inhibitor 9 (PI-9) in MCF-7 human breast cancer cells. By inducing PI-9, genistein inhibits the ability of human natural killer (NK) cells to lyse the target breast cancer cells. In ERalphaHA cells, stably transfected MCF-7 cells, which contain elevated levels of estrogen receptor-alpha (ERalpha), 100 pm genistein or 17beta-estradiol potently induce PI-9 and prevent NK cells from killing the target breast cancer cells. The concentrations of genistein that fully induce PI-9 in MCF-7 cells, and in ERalphaHA cells, are far lower than those previously reported to elicit estrogenic responses through ERalpha. Because 4-hydroxytamoxifen, raloxifene, and ICI 182,780/Faslodex all block genistein induction of PI-9 and elevated levels of ERalpha enhance induction of PI-9, genistein acts via ERalpha to induce PI-9. Increasing levels of ERalpha in breast cancer cells results in a progressive increase in induction of PI-9 by genistein and in the cell's ability to evade killing by NK cells. Moderate levels of dietary genistein and soy flour effectively induce PI-9 in human breast cancers grown in ovariectomized athymic mice. A significant population consumes levels of genistein in soy products that may be high enough to induce PI-9, perhaps potentiating the survival of some preexisting breast cancers by enabling them to evade immunosurveillance.
A nanohybrid consisting of water-soluble thioglycolic acid (TGA)-capped CdTe nanocrystals (NCs) and methylene blue (MB) was designed as a label-free luminescent signaling platform for DNA. This sensing system was identified to operate under the photoinduced electron transfer (PET) mechanism in which MB is the electron acceptor and the binding site for the designated target molecule DNA. We showed that MB bound with TGA-capped CdTe NCs via strong electrostatic interactions resulted in an efficient quenching of the photoluminescence (PL) of NCs. Steady-state and time-resolved PL, and electron paramagnetic resonance (EPR) experiments established the quenching pathway of PET from the conduction band (CB) of NCs to the ground state of MB. In the presence of the target molecule DNA, the MB-quenched PL of NCs could be reversibly restored by double-stranded DNA as the PET pathway is blocked when MB is taken away from the NCs surface due to its intercalation into, and electrostatic interaction with, DNA. The platform was successfully applied for sensing DNA and signaling DNA hybridization by switching the PET process. Such a nanohybrid represents a robust PET luminescent nanosensor that is, in principle, applicable for other species by employing suitable electron acceptors as binding sites.
Abstract:The relative contents of Cu + and Cu 2+ in solutions of anhydrous Nieuwland catalyst and CuCl 2 -added anhydrous Nieuwland catalyst were detected by X-ray photoelectron spectroscopy (XPS). Results indicated that Cu + could be transformed into Cu 2+ during the process of acetylene dimerization into monovinylacetylene, leading to deactivation of the catalyst. Moreover, the addition of Cu 2+ inhibited the oxidation of Cu + into Cu 2+ and enhanced the performance and lifetime of the catalyst. The optimum molar ratio of Cu + to Cu 2+ was approximately 2:1; at this ratio, up to 40% acetylene conversion may be achieved.
The purpose of the present study was to investigate the role of extracellular matrix proteins (ECMs; collagens I and IV, fibronectin, and laminin) in modulating proliferative responses of normal mammary epithelial cells in serum-free culture to epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I). As EGF and IGF-I can alter steroid responses, the interactions among growth factors, estrogen, and R5020 were also investigated. We report the novel finding that all ECMs tested, but not a nonspecific attachment factor, poly-L-lysine (PL), promoted a highly synergistic proliferative response to EGF plus IGF-I. EGF receptors were significantly increased with culture time on all ECMs, but not on PL. IGF receptor expression was significantly 2- to 4-fold higher on all ECMs compared with PL. EGF decreased IGF-binding protein-2 (IGFBP-2) and IGFBP-3 by more than 50% in the presence of IGF-I on PL or collagen I. These results indicate that ECM-specific IGF-I/EGF synergism occurs in response to ECM up-regulation of growth factor receptors and EGF down-regulation of inhibitory IGFBPs. Growth factors did not synergize with estrogen and/or R5020. Instead, estrogen plus R5020 decreased EGF-plus IGF-I-induced proliferation in an ECM-dependent manner. These studies demonstrate that proliferation of normal mammary epithelial cells involves complex interactions among steroids, growth factors, binding proteins, and ECMs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.