کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151680 | 1090013 | 2011 | 19 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Activation of the Long Terminal Repeat of Human Endogenous Retrovirus K by Melanoma-Specific Transcription Factor MITF-M
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Activation of the Long Terminal Repeat of Human Endogenous Retrovirus K by Melanoma-Specific Transcription Factor MITF-M Activation of the Long Terminal Repeat of Human Endogenous Retrovirus K by Melanoma-Specific Transcription Factor MITF-M](/preview/png/2151680.png)
چکیده انگلیسی
The human and Old World primate genomes possess conserved endogenous retrovirus sequences that have been implicated in evolution, reproduction, and carcinogenesis. Human endogenous retrovirus (HERV)-K with 5â²LTR-gag-pro-pol-env-rec/np9-3â²LTR sequences represents the newest retrovirus family that integrated into the human genome 1 to 5 million years ago. Although a high-level expression of HERV-K in melanomas, breast cancers, and terato-carcinomas has been demonstrated, the mechanism of the lineage-specific activation of the long terminal repeat (LTR) remains obscure. We studied chromosomal HERV-K expression in MeWo melanoma cells in comparison with the basal expression in human embryonic kidney 293 (HEK293) cells. Cloned LTR of HERV-K (HML-2.HOM) was also characterized by mutation and transactivation experiments. We detected multiple transcriptional initiator (Inr) sites in the LTR by rapid amplification of complementary DNA ends (5â² RACE). HEK293 and MeWo showed different Inr usage. The most potent Inr was associated with a TATA box and three binding motifs of microphthalmia-associated transcription factor (MITF). Both chromosomal HERV-K expression and the cloned LTR function were strongly activated in HEK293 by transfection with MITF-M, a melanocyte/melanoma-specific isoform of MITF. Coexpression of MITF and the HERV-K core antigen was detected in retinal pigmented epithelium by an immunofluorescence analysis. Although malignant melanoma lines MeWo, G361, and SK-MEL-28 showed enhanced HERV-K transcription compared with normal melanocytes, the level of MITF-M messenger RNA persisted from normal to transformed melanocytes. Thus, MITF-M may be a prerequisite for the pigmented cell lineage-specific function of HERV-K LTR, leading to the high-level expression in malignant melanomas.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 13, Issue 11, November 2011, Pages 1081-1092, IN36-IN42
Journal: Neoplasia - Volume 13, Issue 11, November 2011, Pages 1081-1092, IN36-IN42
نویسندگان
Iyoko Katoh, Anna MÃrová, Shun-ichi Kurata, Yasushi Murakami, Kenji Horikawa, Natsuko Nakakuki, Takunobu Sakai, Kunihiko Hashimoto, Ayako Maruyama, Takaaki Yonaga, Nahoko Fukunishi, Kohji Moriishi, Hirohisa Hirai,