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学科主题: 临床医学
题名:
Regulatory mechanisms for abnormal expression of the human breast cancer specific gene 1 in breast cancer cells
作者: Lu Aiping; Li Qing; Liu Jingwen
关键词: breast cancer-specific gene 1 ; promoter ; transcriptional activity
刊名: SCIENCE IN CHINA SERIES C-LIFE SCIENCES
发表日期: 2006-08-01
DOI: 10.1007/s11427-006-2006-1
卷: 49, 期:4, 页:403-408
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biology
研究领域[WOS]: Life Sciences & Biomedicine - Other Topics
关键词[WOS]: SYNUCLEIN-GAMMA ; ABERRANT EXPRESSION ; CPG ISLAND ; IDENTIFICATION ; TRANSCRIPTION ; CARCINOMA ; DISEASE
英文摘要:

Breast cancer-specific gene 1 (BCSG1), also referred as synuclein gamma, was originally isolated from a human breast cancer cDNA library and the protein is mainly localized to presynaptic terminals in the nervous system. BCSG1 is not expressed in normal or benign breast lesions, but expressed at an extremely high level in the vast majority of the advanced staged breast carcinomas and ovarian carcinomas. Overexpression of BCSG1 in cancer cells led to significant increase in cell proliferation, motility and invasiveness, and metastasis. To elucidate the molecular mechanism and regulation for abnormal transcription of BCSG1, a variety of BCSG1 promoter luciferase reporters were constructed including 3 ′ end deleted sequences, Sp1 deleted, and activator protein-1 (AP1) domains mutated. Transient transfection assay was used to detect the transcriptional activation of BCSG1 promoters. Results showed that the Sp1 sequence in 5 ′-flanking region was involved in the basal transcriptional activities of BCSG1 without cell-type specificity. In comparison to pGL3-1249, the reporter activities of pGL3-1553 in BCSG1-negative MCF-7 cells and pGL3-1759 in HepG2 cells were notably decreased. Mutations at AP1 sites in BCSG1 intron 1 significantly reduced the promoter activity in all cell lines. Transcription factors, c-jun, c-fos and cyclin AMP-responsive element binding (CREB) protein, could markedly enhance the promoter activities. Thus, our results suggest that the abnormal expression of BCSG1 in breast cancer cells is likely regulated by multiple mechanisms. The 5 ′ flanking region of BCSG1 provides the basal transcriptional activity without cell type specificity. A critical promoter element involved in abnormal expression of BCSG1 presents in the first exon. The cell type specificity of BCSG1 transcription is probably affected through intronic cis-regulatory sequences. AP1 domains in the first intron play an important role in control of BCSG1 transcription.

语种: 英语
WOS记录号: WOS:000240411800013
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60206
Appears in Collections:北京大学临床肿瘤学院_病理科_期刊论文

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作者单位: 1.VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA
2.Peking Univ, Sch Oncol, Beijing Canc Hosp, Dept Pathol, Beijing 100036, Peoples R China

Recommended Citation:
Lu Aiping,Li Qing,Liu Jingwen. Regulatory mechanisms for abnormal expression of the human breast cancer specific gene 1 in breast cancer cells[J]. SCIENCE IN CHINA SERIES C-LIFE SCIENCES,2006,49(4):403-408.
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