@article{75e43e4efad9420eabb254d347ca016c,
title = "Structure of the int-5, a novel MMTV integration genomic locus containing mouse early transposon LTR homology region",
abstract = "Previous studies have reported the cloning and identification of the int-5, a novel mouse mammary tumor virus (MMTV) integration locus involved in mammary tumorigenesis. Here we report the characterization of the 5.5 kb region from this novel MMTV integration site. Our results show that the region after the MMTV integration site, a 258 bp sequence is homologous (100%) to the mouse early transposon (mETn) long-terminal repeat and other sequences of the this transposon are not present in the 5.5 kb region. Our results also show for the first time the tumor specific expression of mETn and expression of the region downstream of the MMTV integration site that is homologous to mETn-LTR in D2 mammary tumors.",
keywords = "(Mouse), Early transposon, Mammary tumor, int gene, mETn expressing",
author = "Durgam, {Vijayender Rao} and Easton, {John A.} and Ramana Surya and Tekmal, {Rajeshwar Rao}",
note = "Funding Information: is not clear and needs further detailed investigation. This is the first demonstration of expression of mETn sequences in mammary tumors. To demonstrate that the integration of MMTV in the 3{\textquoteright} untranslated region of the aromatase gene in the int-5 locus results in the expression of an aberrant transcript, we examined the expression of this region using reverse transcription and polymerase chain reaction (RT-PCR). We designed the PCR primers in a such a way that the region from the MMTV integration site to mETn is amplified. The schematic location of these primers, their sequence and data are presented in Fig. 3. Our results clearly show the amplification of the expected 762 bp RT-PCR product only from D2 tumor mRNA but not from normal BALB/c mammary gland mRNA or other controls, confirming the expression of the aberrant transcript from downstream of the MMTV integration site of the int-5 locus. These results demonstrates that MMTV integration in the 3{\textquoteright} untranslated region of the aromatase gene leads to the expression of the aberrant transcript that includes flanking region next to known aromatase gene sequences. This observation raises a very interesting possible mechanism for the tumor specific overexpression of int-.5/aromatase in BALB/c D2 mammary tumors. MMTV integration in the aromatase 3{\textquoteright} untranslated region leads to the formation of an aberrant int5/aromatase mRNA transcript. This change in the 3{\textquoteright} untranslated region may enhance the stability of the int-_5/aromatase mRNA leading to the accumulation of this message, or increase the translatability of this message in mammary tumors. Similar mechanisms exit with other int genes. For example, MMTV proviral insertion at the 3{\textquoteright} end of int-2 causes a change in the 3{\textquoteright} end of the transcript this gene [17]. Whether the formation of an aberrant transcript by int-5 / aromatase gene as the result of MMTV integration has any direct role in the initiation of mammary tumorigenesis needs further examination. This study was supported by the National Institutes of Health grant CA57559.",
year = "1995",
month = jul,
day = "25",
doi = "10.1016/0167-4781(95)00093-V",
language = "English (US)",
volume = "1263",
pages = "89--92",
journal = "BBA - Gene Structure and Expression",
issn = "0167-4781",
publisher = "Elsevier B.V.",
number = "1",
}