Lani
05-19-2012, 12:02 AM
they are getting closer to finding out and this might really help find better drugs to stop/prevent her2+ breast cancer
This article shows that a histone (a covering of DNA which can hide the underlying DNA "genes" from being translated/made into proteins) may cover a suppressor of transcription(the reading of the DNA in a way to allow the making of a "negative"** copy which then allows the protein to be made from that -thus allowing gross overactivity of the her2 gene making many, too many, of the her2 receptor (the protein gene product)
Dr. Slamon usually says each cell makes about 2 million of them when a normal cell may have perhaps twenty!
** negative as in a negative of a photograph. the gene is what is photographed, the mRNA is the negative and the protein gene product (here the her2 receptor) is the finished photograph which is the opposite of the negative
J Biol Chem. 2012 May 14. [Epub ahead of print]
The atypical histone macroH2A1.2 interacts with HER-2 in cancer cells.
Li X, Kuang J, Shen Y, Majer MM, Nelson CC, Parsawar K, Heichman KA, Kuwada SK.
Source
U of Hawaii, United States;
Abstract
Since HER-2 has been demonstrated in the nuclei of cancer cells we hypothesized that it might interact with transcription factors that activate ERBB2 transcription. macroHistone 2A1 (H2AFY; mH2A1) was found to interact with HER-2 in cancer cells that overexpress HER-2. Of the two human mH2A1 isoforms, mH2A1.2, but not mH2A1.1, interacted with HER-2 in human cancer cell lines. Overexpression of mH2A1.2, but not mH2A1.1, in cancer cells significantly increased HER-2 expression and tumorigenicity. Inhibition of HER-2 kinase activity diminished mH2A1 expression and mH2A1.2-induced ERBB2 transcription in cancer cells. Chromatin immunoprecipitation of mH2A1.2 in cancer cells stably transfected with mH2A1.2 showed enrichment of mH2A1.2 at the HER-2 promoter suggesting a role for mH2A1.2 in driving HER-2 overexpression. The evolutionarily conserved macro domain of mH2A1.2 was sufficient for the interaction between HER-2 and mH2A1.2, and, for mH2A1.2-induced ERBB2 transcription. Within the macro domain of mH2A1.2, a trinucleotide insertion (-eis) sequence not found in mH2A1.1 was essential for the interaction between HER-2 and mH2A1.2 as well as mH2A1.2-induced HER-2 expression and cell proliferation.
PMID: 22589551
This article shows that a histone (a covering of DNA which can hide the underlying DNA "genes" from being translated/made into proteins) may cover a suppressor of transcription(the reading of the DNA in a way to allow the making of a "negative"** copy which then allows the protein to be made from that -thus allowing gross overactivity of the her2 gene making many, too many, of the her2 receptor (the protein gene product)
Dr. Slamon usually says each cell makes about 2 million of them when a normal cell may have perhaps twenty!
** negative as in a negative of a photograph. the gene is what is photographed, the mRNA is the negative and the protein gene product (here the her2 receptor) is the finished photograph which is the opposite of the negative
J Biol Chem. 2012 May 14. [Epub ahead of print]
The atypical histone macroH2A1.2 interacts with HER-2 in cancer cells.
Li X, Kuang J, Shen Y, Majer MM, Nelson CC, Parsawar K, Heichman KA, Kuwada SK.
Source
U of Hawaii, United States;
Abstract
Since HER-2 has been demonstrated in the nuclei of cancer cells we hypothesized that it might interact with transcription factors that activate ERBB2 transcription. macroHistone 2A1 (H2AFY; mH2A1) was found to interact with HER-2 in cancer cells that overexpress HER-2. Of the two human mH2A1 isoforms, mH2A1.2, but not mH2A1.1, interacted with HER-2 in human cancer cell lines. Overexpression of mH2A1.2, but not mH2A1.1, in cancer cells significantly increased HER-2 expression and tumorigenicity. Inhibition of HER-2 kinase activity diminished mH2A1 expression and mH2A1.2-induced ERBB2 transcription in cancer cells. Chromatin immunoprecipitation of mH2A1.2 in cancer cells stably transfected with mH2A1.2 showed enrichment of mH2A1.2 at the HER-2 promoter suggesting a role for mH2A1.2 in driving HER-2 overexpression. The evolutionarily conserved macro domain of mH2A1.2 was sufficient for the interaction between HER-2 and mH2A1.2, and, for mH2A1.2-induced ERBB2 transcription. Within the macro domain of mH2A1.2, a trinucleotide insertion (-eis) sequence not found in mH2A1.1 was essential for the interaction between HER-2 and mH2A1.2 as well as mH2A1.2-induced HER-2 expression and cell proliferation.
PMID: 22589551