171,286 research outputs found
Hormone Involvement in Tissue Development, Physiology and Oncogenesis: A Preface to the Special Issue
No full textHormones, i.e., the products of specialized endocrine cells which spread throughout the body via the bloodstream, control the normal development and growth of organisms at the embryo-fetal stage and, in adult life, regulate, integrate, and coordinate a range of different physiological processes which concern virtually all body tissues. They exert their biological effects by interacting with either surface or intracellular receptors, thereby activating signalization pathways [1]. For example, steroid hormones, such as those released by the adrenal glands, testes and ovaries, once freely crossed through
the plasmalemma, bind to receptors that act as ligand-dependent transcriptional regulators and influence the expression of a plethora of target genes responsible for diversified biological responses, including sexual differentiation, osmoregulation, metabolism and developmental roles in various fetal
systems among others [2,3]
Midregion PTHrP and Human Breast Cancer Cells
No full textPTHrP is a polyhormone undergoing proteolytic processing into smaller bioactive forms, comprising an N-terminal peptide, which is the mediator of the “classical” PTH-like effect, as well as midregion and C-terminal peptides. The midregion PTHrP domain (38-94)-amide was found to restrain growth and invasion in vitro of some breast cancer cell lines, causing striking toxicity and accelerating death; the most responsive being MDA-MB231, whose tumorigenesis was also attenuated in vivo. In addition, midregion PTHrP appears to be imported in the nucleoplasm of cultured MDA-MB231 cells and in vitro, it can bind chromatin of metaphase spread preparations and also an isolated 20-mer oligonucleotide, thereby appearing endowed with a putative transcription factor–like DNA-binding ability. The object of this review is to discuss collectively and critically both precedent and more updated data obtained in the lab, the latter arising from assays on DNA status, and gene and protein expression patterns of treated cells, aiming to check whether the cytotoxicity of the peptide may result from a reprogramming of gene expression towards apoptotic death or, instead, it is to be ascribed to an unprogrammed perturbation of cell functions
Breast cancer cell growth/motility is influenced by metal compounds
No full textTriple-negative breast cancer (TNBC) is a highly "aggressive" malignant neoplasm with limited treatment options due to the lack of expression of estrogen and progesterone receptors and HER2/neu. In search of novel molecules displaying anti-TNBC activities, the TNBC cell line MDA-MB231 was exposed to cadmium chloride and/or manganese chloride, and a biological characterization of the effect observed was performed. The data obtained demonstrate a cytotoxic effect exerted by cadmium chloride with drastic changes affecting gene expressions and production of reactive oxygen species. Conversely, manganese chloride was effective in increasing cell number and promoting cell invasive ability. Such effect was reverted by coexposure with cadmium chloride. Thus, metal compounds appear to be able to modulate the biological behavior of TNBC cells, although addressing them to different fates. The data obtained suggest that high environmental pollution with manganese chloride might increase the risk of breast tumorigenesis. On the other hand, the restraining modulatory property of cadmium chloride looks promising and deserves a more detailed mechanistic study aimed to the identification of possible molecular targets instrumental in inhibiting the expansion of malignant breast cancer
Parathyroid hormone-related protein (PTHrP): a key regulator of life/death decisions by tumor cells with potential clinical applications
No full textParathyroid hormone-related protein (PTHrP), classically regarded as the mediator of the humoral hypercalcemia of malignancy syndrome, is a polyhormone that undergoes proteolytic processing into smaller bioactive forms. These bioactive forms comprise an N-terminal- as well as midregion- and C-terminal peptides, which have been shown to regulate various biological events, such as survival, proliferation and differentiation, in diverse cell model systems, both normal and pathological. A number of experimental data have demonstrated that PTHrP is also able to modulate tumor-relevant phenotypic expressions, thereby playing a role in early and advanced tumorigenesis, and in the response to treatment. In particular, interest has mainly been focused on the effects of PTHrP on cell proliferation/apoptosis, migration and invasion, which are the main roles involved in cancer development in vivo. The objective of this review is to discuss collectively the literature data on the molecular and biochemical basis of the mechanisms underlying the different, and sometimes opposite, effects exerted by PTHrP on various neoplastic cytotypes, with some final comments on both present and potential utilization of PTHrP as a target for anti-cancer therapy
Espressione cadmio-dipendente di AEG-1, c-fos e c-jun in cellule tumorali mammarie umane
No full textHistone Deacetylase Inhibitors
No full textHistone deacetylases (HDACs) are key components of the epigenetic machinery controlling gene expression. They are involved in chromatin remodeling events via post-translational histone modifications but may also act on nonhistone proteins, influencing many fundamental cellular processes. Due to the key involvement of HDACs in serious human pathologies, including cancer, HDAC inhibitors (HDACis) have received increased attention in recent years. It is known that marine invertebrates produce significant amounts of secondary metabolites showing active pharmacological properties and an extensive spectrum of biomedical applications. Some of these compounds possess HDACi properties
Collagen-induced differential expression of an RNA polymerase subunit by breast cancer cells
No full textIt was previously reported that the stroma of ductal infiltrating carcinoma (DIC) of the human breast contains considerable amount of an embryo-foetal collagen type, OF/LB (onco-foetal/laminin-binding), and that adhesion of 8701-BC DIC cells onto OF/LB collagen substrates selectively promotes cell growth, motility, production of extracellular lytic enzymes and invasion "in vitro" if compared with other collagen species. To detect possible transcriptional differences for regulatory proteins following OF/LB collagen-cell interactions, we submitted RNA preparations from 8701-BC cells grown on collagen type I, IV and OF/LB to "differential display"-PCR in the presence of degenerate C(2)H(2) zinc finger and protein tyrosine kinase domain oligonucleotide primers. We report that growth of 8701-BC cells on OF/LB collagen is consistently associated with the up-regulation of hRPB17 gene, coding for an RNA polymerase subunit, as confirmed by conventional RT-PCR and Northern analyses
Type V Collagen and Protein Kinase C eta Down-Regulation in 8701-BC Breast Cancer Cells
No full textWe previously reported that ductal infiltrating carcinomas (d.i.c.) of the human breast display profound modifications
of the stromal architecture, associated with anomalous collagen composition. Among the major alterations
observed in the interstitial collagen, the relative increase of type V collagen content was detected. When type V
collagen was used as an ‘‘in vitro’’ substrate for 8701-BC d.i.c. cells, it appeared able to restrain cell growth, inhibit
cell motility and invasion ‘‘in vitro’’, and modify the expression levels of genes coding for apoptosis factors, caspases
and stress response proteins. In the present paper we demonstrate that type V collagen induces the down-regulation
of protein kinase C eta, an event that may be, at least in part, responsible of the previously-reported modifications of
cell morphology and growth rate, and that appears to be involved in the already-observed changes of expression levels
of genes encoding for anti- (Bcl-2) and pro-apoptotic factors (Bad, Dapk, Bcl-Xs) and enzymes (caspase 5 and 8)
Collagen changes in the extracellular matrix of tumor-affected human breast: a tale of OF/LB and type V collagens
No full textIt is widely acknowledged that the extracellular matrix (ECM) ofconnective tissues plays active roles in numerous biological processessuch as cell differentiation, life/death promotion and carcinogenesis.Ductal infiltrating carcinoma (DIC) of the breast is a highly metastatictumor histotype commonly associated with drastic massive alterations ofECM architecture and composition, especially concerning its collagenouscomponent. In particular, it was demonstrated that the stroma of DIC ofthe human breast contains a considerable amount of an embryo-foetalcollagen type (OF/LB), while type V collagen, which is a minorcomponent of normal human breast ECM, undergoes over-deposition inthe affected gland. In vitro studies indicated that substrates made fromthese collagen species were able to exert a marked and opposite effect onviability, proliferation and invasiveness of DIC-derived breast cancer celllines. In this chapter, we will summarize and discuss the studies on OF/LB and type V collagens and their putative relevance in DIC ingrowth
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