Post-transcriptional regulation of metallothionein isoform 1 and 2 expression in the human breast and the MCF-10A cell line

Studies have shown, using immunohistochemical staining, that the MT-1 and MT-2 proteins (MT-1/2) are overexpressed in a substantial subset of ductal breast cancers, that overexpression occurs early in the disease process, and that this overexpression is indicative of a poor prognosis. Normal ductal...

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Vydané v:Toxicological sciences Ročník 85; číslo 2; s. 906
Hlavní autori: Gurel, Volkan, Sens, Donald A, Somji, Seema, Garrett, Scott H, Weiland, Tim, Sens, Mary Ann
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.06.2005
Predmet:
Breast - metabolism
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cadmium - toxicity
Cell Line, Tumor
Cell Survival - drug effects
Epithelium - metabolism
Female
Gene Expression Regulation - physiology
Humans
Immunohistochemistry
Metallothionein - biosynthesis
Metallothionein - genetics
Neoplasm Proteins - biosynthesis
Paraffin Embedding
Protein Processing, Post-Translational - physiology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
ISSN:1096-6080
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Shrnutí:Studies have shown, using immunohistochemical staining, that the MT-1 and MT-2 proteins (MT-1/2) are overexpressed in a substantial subset of ductal breast cancers, that overexpression occurs early in the disease process, and that this overexpression is indicative of a poor prognosis. Normal ductal breast epithelium fails to immunostain for the MT-1/2 protein, whereas the myoepithelial cells of the ducts stain intensely. There is no information regarding the expression of the mRNAs for the eight active MT-1 and MT-2 genes in normal breast duct epithelium. Microdissection of normal breast samples was used to obtain total RNA from enriched populations of ductal epithelium and myoepithelium. Analysis by reverse-transcription polymerase chain reaction (RT-PCR) demonstrated that the identity of the MT isoform-specific genes expressed (MT-2A and MT-1X) and their relative levels of expression were similar between the myoepithelial and ductal components. These findings indicate that the ductal and myoepithelial components express similar amounts of MT-2A and MT-1X mRNAs, but that they have distinctly different expression of the MT-1/2 protein. Confluent cultures of MCF-10A breast epithelial cells were exposed to Cd(+2) to test for evidence of post-transcriptional regulation of MT-1/2 protein accumulation in ductal epithelium. It was demonstrated that Cd(+2) elicited only a marginal induction of MT-1E, MT-1X, or MT-2A mRNAs, whereas, there was a marked increase in MT-1/2 protein, reaching levels of 6% of total cell protein under conditions of extended exposure. This study suggests that the mechanism underlying the finding of increased MT-1/2 protein expression in ductal breast cancer may involve, to some degree, the post-transcriptional regulation of MT-1/2 protein expression.
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content type line 23
ISSN:1096-6080
DOI:10.1093/toxsci/kfi155