Immunoglobulins （Igs） are known to be synthesized and secreted only by B lymphocytes. Class switch recombination （CSR） is a key event that enables B cells to express Igs, and one of the crucial steps for CSR initi...Immunoglobulins （Igs） are known to be synthesized and secreted only by B lymphocytes. Class switch recombination （CSR） is a key event that enables B cells to express Igs, and one of the crucial steps for CSR initiation is the germline transcription of Iggenes. Surprisingly, recent studies have demonstrated that the Iggenes are also expressed in some epithelial cancer cells; however, the mechanisms underlying how cancer cells initiate CSR and express Igs are still unknown. In this study, we confirmed that the Ig la I promoter in cancer cell lines was activated by the Ets- 1 transcription factor, and the activity of the Ig la I promoter and ig lal-C^l germiine transcription were attenuated after knockdown of Ets-1 by specific small interfering RNAs （siRNA）. Furthermore, the expression of Ets-1 and Iga heavy chain in cancer cells was dose dependently upregulated by TGF-I^I. These results indicate that activation of the Ig lal promoter by the transcriotion factor Ets-1 is a critical Dathwav and orovides a novel mechanism for le exoression in non-B cell cancers.展开更多
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...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 2800 to 2610 bp and a copromoter-like element at 2610 to 2300 bp,were identified in two epithelial cancer cell lines,HeLa S3 and HT-29.The octamer element(59-ATGCAAAT-39)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.展开更多
文摘Immunoglobulins （Igs） are known to be synthesized and secreted only by B lymphocytes. Class switch recombination （CSR） is a key event that enables B cells to express Igs, and one of the crucial steps for CSR initiation is the germline transcription of Iggenes. Surprisingly, recent studies have demonstrated that the Iggenes are also expressed in some epithelial cancer cells; however, the mechanisms underlying how cancer cells initiate CSR and express Igs are still unknown. In this study, we confirmed that the Ig la I promoter in cancer cell lines was activated by the Ets- 1 transcription factor, and the activity of the Ig la I promoter and ig lal-C^l germiine transcription were attenuated after knockdown of Ets-1 by specific small interfering RNAs （siRNA）. Furthermore, the expression of Ets-1 and Iga heavy chain in cancer cells was dose dependently upregulated by TGF-I^I. These results indicate that activation of the Ig lal promoter by the transcriotion factor Ets-1 is a critical Dathwav and orovides a novel mechanism for le exoression in non-B cell cancers.
基金supported by Fundamental Research Grants 30572094 and 30772470 from the Natural Sciences Foundation,China.We thank Dr Dalong Ma and Dr Mingxu Xu(Peking University Center for Human Disease Genomics)for their comments and suggestions.This manuscript was proofread by an English-speaking professional with a science background at Elixigen Corporation.
文摘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 2800 to 2610 bp and a copromoter-like element at 2610 to 2300 bp,were identified in two epithelial cancer cell lines,HeLa S3 and HT-29.The octamer element(59-ATGCAAAT-39)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.
