PubMed · 13772944
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E S MORTENSEN. 1961-06-16. [Hypercalcemic nephropathy].. https://pubmed.ncbi.nlm.nih.gov/13772944/
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To identify genes that are differentially expressed in human esophageal squamous cell carcinoma (ESCC), we have developed a cDNA microarray representing 34 176 clones to analyse gene expression profiles in ESCC. A total of 77 genes (including 31 novel genes) were downregulated, and 15 genes (including one novel gene) were upregulated in cancer tissues compared with their normal counterparts. Immunohistochemistry and Northern blot analysis were carried out to verify the cDNA microarray results. It was revealed that genes involved in squamous cell differentiation were coordinately downregulated, including annexin I, small proline-rich proteins (SPRRs), calcium-binding S100 proteins (S100A8, S100A9), transglutaminase (TGM3), cytokeratins (KRT4, KRT13), gut-enriched Krupple-like factor (GKLF) and cystatin A. Interestingly, most of the downregulated genes encoded Ca(2+)-binding or -modulating proteins that constitute the cell envelope (CE). Moreover, genes associated with invasion or proliferation were upregulated, including genes such as fibronectin, secreted protein acidic and rich in cystein (SPARC), cathepsin B and KRT17. Functional analysis of the alteration in the expression of GKLF suggested that GKLF might be able to regulate the expression of SPRR1A, SPRR2A and KRT4 in ESCC. This study provides new insights into the role of squamous cell differentiation-associated genes in ESCC initiation and progression.
PRL (prolactin) has been implicated in the proliferation and differentiation of numerous tissues, including the prostate gland. However, the PRL-R (PRL receptor) signal transduction pathway, leading to the stimulation of cell proliferation, remains unclear and has yet to be mapped. The present study was undertaken to develop a clear understanding of the mechanisms involved in this pathway and, in particular, to determine the role of K(+) channels. We used androgen-sensitive prostate cancer (LNCaP) cells whose proliferation is known to be stimulated by PRL. Reverse transcriptase PCR analysis showed that LNCaP cells express a long form of PRL-R, but do not produce its intermediate isoform. Patch-clamp techniques showed that the application of 5 nM PRL increased both the macroscopic K(+) current amplitude and the single K(+)-channel open probability. This single-channel activity increase was reduced by the tyrosine kinase inhibitors genistein, herbimycin A and lavandustine A, thereby indicating that tyrosine kinase phosphorylation is required in PRL-induced K(+) channel stimulation. PRL enhances p59( fyn ) phosphorylation by a factor of 2 after a 10 min application in culture. In addition, where an antip59( fyn ) antibody is present in the patch pipette, PRL no longer increases K(+) current amplitude. Furthermore, the PRL-stimulated proliferation is inhibited by the K(+) channel inhibitors alpha-dendrotoxin and tetraethylammonium. Thus, as K(+) channels are known to be involved in LNCaP cell proliferation, we suggest that K(+) channel modulation by PRL, via p59( fyn ) pathway, is the primary ionic event in PRL signal transduction, triggering cell proliferation.
Methacryloyloxyethyl phosphate is a methacrylic monomer used to modify different substrates by copolymerisation, in order to enhance hydroxyapatite deposition onto their surfaces. We report the synthesis of two copolymers series using increasing concentrations of methacryloyloxyethyl phosphate with (diethylamino) ethyl methacrylate and 1-vinyl-2-pyrrolidinone. Reactivity ratios were evaluated for the two copolymer systems. The influence of phosphate content and distribution on the capacity to form a calcium-rich layer was evaluated after immersion for 15 days in a synthetic body fluid. Corresponding homopolymers were synthesised as controls. Calcium-phosphorus globules were developed only on samples containing (diethylamino) ethyl methacrylate, and presenting a low density of phosphate groups. The amounts of calcium increased when higher concentrations of methacryloyloxyethyl phosphate were used. The use of 1-vinyl-2-pyrrolidinone was associated with greater calcium amounts, (compared to (diethylamino) ethyl methacrylate). The amine groups may favour the attraction of phosphorus, thus creating another way for the nucleation of calcium/phosphate crystals.