Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metallothionein (MT), a low-molecular weight protein with pleiotropic functions, is believed to play an important role in tumorigenesis. The aim of this study was to compare the expression of functional MT-1 and MT-2 mRNA isoforms in five breast cancer cell lines ranging from noninvasive MCF7 breast cancer cells to highly aggressive MDA-MB-231 breast cancer cells together with breast myoepithelial cells in vitro by conventional semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR. The MT-2A isoform was observed to be differentially upregulated in the invasive phenotype. The MT-1E isoform was found to be present in estrogen receptor-negative breast cancer cell lines (MDA-MB-231 and Hs578T) but not detectable in the estrogen receptor-positive cell lines (T47D, MCF7, and ZR75-1 cells). Only the myoepithelial cells exhibited the presence of the MT-1G transcript. Direct sequencing of the RT-PCR products revealed the occurrence of a variant MT-1H isoform with changes in amino acid residues in the protein sequence and notable differences in the predicted secondary protein structure. The observations in this study are relevant to the development of novel approaches to metastatic breast cancer disease, and may herald the search for novel MT mutants and the elucidation of their biological roles.
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PMID:Differential expression of metallothionein 1 and 2 isoforms in breast cancer lines with different invasive potential: identification of a novel nonsilent metallothionein-1H mutant variant. 1457

The induction of CYP1A1 expression by oltipraz, a synthetic chemo-preventive agent, which increases intracellular calcium concentration, has previously been shown to result from transcriptional activation of CYP1A1 gene mediated by the Ah receptor (AhR), although oltipraz does not bind the receptor. The present study investigated the possible mechanisms of oltipraz-induced activation of AhR and the subsequent induction of CYP1A1 transcription. Treatment of the human metastatic breast cancer cell line MT-2 with oltipraz results in a concentration-dependent increase in the activity of the calcium-dependent calpain, as measured towards the BOC-LM-CMAC fluorescent substrate. This increase in calpain activity was coupled with the AhR activation, as evidenced by its nuclear localization and increased transcription of CYP1A1 gene. Treatment of cells with calpain specific inhibitor MDL 28170 completely blocked the oltipraz-induced nuclear translocation of AhR and subsequent CYP1A1 expression. Furthermore, treatment with oltipraz resulted in the classical ligand-dependent down-regulation of AhR protein, in a concentration dependent manner. The presented data established for the first time a mechanism of activating AhR and its transcription of CYP1A1 by oltipraz through activation of calcium-dependent calpain.
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PMID:The induction of CYP1A1 by oltipraz is mediated through calcium-dependent-calpain. 1689 Oct 67