Distinct regulatory mechanism of immunoglobulin gene transcription in epithelial cancer cells.
The restriction of immunoglobulin (Ig) expression to B lymphocytes is well established. However, several reports have confirmed that the Ig gene can be expressed in many non-B cancer cells and/or some normal cells. Our aim is to determine whether the Ig gene promoter can be activated in non-B cancer cells and to identify the regulatory mechanism for Ig gene expression. Our results show that the Ig promoter of VH4-59 was activated in several non-B cancer cell lines. Moreover, two novel positive regulatory elements, an enhancer-like element at -800 to -610 bp and a copromoter-like element at -610 to -300 bp, were identified in two epithelial cancer cell lines, HeLa S3 and HT-29. The octamer element (5'-ATGCAAAT-3') located in the Ig promoter, a crucial element for B-cell-derived Ig gene transcription, was also very important for non-B-cell-derived Ig gene transcription. More importantly, we confirmed that octamer-related protein-1 (Oct-1), but not Oct-2, was a crucial transcriptional factor for Ig gene transcription due to its ability to bind to the octamer element of the Ig promoter in epithelial cancer cells. These results suggested the presence of a distinct regulatory mechanism for Ig gene expression in non-B cancer cells.
Zhu
Xiaohui
X
Peking University Center for Human Disease Genomics, Beijing, China.
Wu
Lina
L
Zhang
Li
L
Hao
Peng
P
Zhang
Shuai
S
Huang
Jing
J
Zheng
Jie
J
Liu
Yinan
Y
Li
Wenjun
W
Zhang
Yingmei
Y
Zhou
Chunyan
C
Zhang
Youhui
Y
Yin
C Cameron
CC
Qiu
Xiaoyan
X
D024506:5' Flanking Region / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D005803:Genes, Immunoglobulin / Q000235:genetics*; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology*; D050811:Octamer Transcription Factor-1 / Q000378:metabolism; D050813:Octamer Transcription Factor-2 / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D014158:Transcription, Genetic
D050811:Octamer Transcription Factor-1; D050813:Octamer Transcription Factor-2; C494165:POU2F1 protein, human; C058435:POU2F2 protein, human
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