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cAMP responsive element binding protein-1 is a transcription factor of lysosomal-associated protein transmembrane-4 Beta in human breast cancer cells.

Zhang M, Xu JJ, Zhou RL, Zhang QY - PLoS ONE (2013)

Bottom Line: Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a potential proto-oncogene, whose overexpression is involved in cancer occurrence and progression.However, its transcriptional regulation mechanism is still unclear.The +10+292 promoter region was possessed the highest transcriptional activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical laboratory, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.

ABSTRACT
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a potential proto-oncogene, whose overexpression is involved in cancer occurrence and progression. Its transcript is up-regulated in various types of solid tumors including breast cancer. However, its transcriptional regulation mechanism is still unclear. To investigate the mechanism of transcriptional regulation of LAPTM4B in human breast cancer cells, a series of luciferase reporter constructs and construct with mutated binding site for cAMP responsive element binding protein-1 (CREB1) were generated by PCR amplification and transiently transfected into breast cancer cells to determine the transcriptional activities of different promoter regions. The +10+292 promoter region was possessed the highest transcriptional activity. The ability of CREB1 to bind the LAPMT4B promoter was confirmed by electrophoretic mobility shift assay, super-shift and RNA interference experiments. Our study identified the core promoter region responsible for constitutive expression of LAPTM4B and clarified that CREB1 played an important role in LAPTM4B transcriptional regulation in human breast cancer cells.

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Related in: MedlinePlus

The schema of forecasting transcription factor in the human LAPTM4B −200∼+301 promoter region.The transcription start site depicted as right-point arrow. The relative scores predicted by JASPAR website online programs were registered under transcription factors name.
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pone-0057520-g001: The schema of forecasting transcription factor in the human LAPTM4B −200∼+301 promoter region.The transcription start site depicted as right-point arrow. The relative scores predicted by JASPAR website online programs were registered under transcription factors name.

Mentions: To explore the cis-acting element covering LAPTM4B promoter region, a 501 bp genomic DNA fragment (region from base 98787609 to 98788109 in the Homo sapiens chromosome 8 genomic contig) was analyzed. The LAPTM4B promoter region appears to be a G/C-rich promoter lacking canonical TATA box, CCAAT, and initiator elements. By computer analysis, potential binding sites for SP1, CREB1, Myf and Klf4 etc were found in the human LAPTM4B −200∼+301 promoter region (Fig. 1). The CREB1 gets the highest relative score among the transcription factors. After analyzing the LAPTM4B transcription initiation sites upstream and downstream of other seven species, we also found the CREB1 binding site in LAPTM4B promoter region in all the 7 vertebrate (Text S1).


cAMP responsive element binding protein-1 is a transcription factor of lysosomal-associated protein transmembrane-4 Beta in human breast cancer cells.

Zhang M, Xu JJ, Zhou RL, Zhang QY - PLoS ONE (2013)

The schema of forecasting transcription factor in the human LAPTM4B −200∼+301 promoter region.The transcription start site depicted as right-point arrow. The relative scores predicted by JASPAR website online programs were registered under transcription factors name.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585361&req=5

pone-0057520-g001: The schema of forecasting transcription factor in the human LAPTM4B −200∼+301 promoter region.The transcription start site depicted as right-point arrow. The relative scores predicted by JASPAR website online programs were registered under transcription factors name.
Mentions: To explore the cis-acting element covering LAPTM4B promoter region, a 501 bp genomic DNA fragment (region from base 98787609 to 98788109 in the Homo sapiens chromosome 8 genomic contig) was analyzed. The LAPTM4B promoter region appears to be a G/C-rich promoter lacking canonical TATA box, CCAAT, and initiator elements. By computer analysis, potential binding sites for SP1, CREB1, Myf and Klf4 etc were found in the human LAPTM4B −200∼+301 promoter region (Fig. 1). The CREB1 gets the highest relative score among the transcription factors. After analyzing the LAPTM4B transcription initiation sites upstream and downstream of other seven species, we also found the CREB1 binding site in LAPTM4B promoter region in all the 7 vertebrate (Text S1).

Bottom Line: Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a potential proto-oncogene, whose overexpression is involved in cancer occurrence and progression.However, its transcriptional regulation mechanism is still unclear.The +10+292 promoter region was possessed the highest transcriptional activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical laboratory, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.

ABSTRACT
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a potential proto-oncogene, whose overexpression is involved in cancer occurrence and progression. Its transcript is up-regulated in various types of solid tumors including breast cancer. However, its transcriptional regulation mechanism is still unclear. To investigate the mechanism of transcriptional regulation of LAPTM4B in human breast cancer cells, a series of luciferase reporter constructs and construct with mutated binding site for cAMP responsive element binding protein-1 (CREB1) were generated by PCR amplification and transiently transfected into breast cancer cells to determine the transcriptional activities of different promoter regions. The +10+292 promoter region was possessed the highest transcriptional activity. The ability of CREB1 to bind the LAPMT4B promoter was confirmed by electrophoretic mobility shift assay, super-shift and RNA interference experiments. Our study identified the core promoter region responsible for constitutive expression of LAPTM4B and clarified that CREB1 played an important role in LAPTM4B transcriptional regulation in human breast cancer cells.

Show MeSH
Related in: MedlinePlus