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Transcription factors E2A, FOXO1 and FOXP1 regulate recombination activating gene expression in cancer cells.

Chen Z, Xiao Y, Zhang J, Li J, Liu Y, Zhao Y, Ma C, Luo J, Qiu Y, Huang G, Korteweg C, Gu J - PLoS ONE (2011)

Bottom Line: It has long been accepted that immunoglobulins (Igs) were produced by B lymphoid cells only.Chromatin immunoprecipitation experiments showed acetylation of RAG enhancer (Erag) and E2A, FOXO1 or FOXP1 were bound to Erag in vivo.These results indicate that in these cancer cells the transcription factors E2A, FOXO1 and FOXP1 regulate RAG expression, which initiates Ig gene rearrangement much in the way similar to B lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Shantou University Medical College, Shantou, China.

ABSTRACT
It has long been accepted that immunoglobulins (Igs) were produced by B lymphoid cells only. Recently Igs have been found to be expressed in various human cancer cells and promote tumor growth. Recombination activating gene 1 (RAG1) and RAG2, which are essential enzymes for initiating variable-diversity-joining segment recombination, have also been found to be expressed in cancer cells. However, the mechanism of RAG activation in these cancer cells has not been elucidated. Here, we investigated the regulatory mechanism of RAG expression in four human cancer cell lines by analyzing transcription factors that induce RAG activation in B cells. By RT-PCR, Western blot and immunofluorescence, we found that transcription factors E2A, FOXO1 and FOXP1 were expressed and localized to the nuclei of these cancer cells. Over-expression of E2A, FOXO1 or Foxp1 increased RAG expression, while RNA interference of E2A, FOXO1 or FOXP1 decreased RAG expression in the cancer cells. Chromatin immunoprecipitation experiments showed acetylation of RAG enhancer (Erag) and E2A, FOXO1 or FOXP1 were bound to Erag in vivo. These results indicate that in these cancer cells the transcription factors E2A, FOXO1 and FOXP1 regulate RAG expression, which initiates Ig gene rearrangement much in the way similar to B lymphocytes.

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Gene transcript expression of Ikaros, PAX5β, NF-κB, E2A, FOXO1 and FOXP1 in cancer cell lines.18S was used as an internal control. Raji was used as a positive control. DNase treated RNA without adding reverse transcriptase was used as a negative control.
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pone-0020475-g001: Gene transcript expression of Ikaros, PAX5β, NF-κB, E2A, FOXO1 and FOXP1 in cancer cell lines.18S was used as an internal control. Raji was used as a positive control. DNase treated RNA without adding reverse transcriptase was used as a negative control.

Mentions: RT-PCR results showed that FOXO1, FOXP1, NF-κB subunit p65 and both of the two isoforms of E2A (E47 and E12), were expressed in the cancer cells A549, PC3, MCF-7 and MDA-MB-231 (Figure 1). However, neither Ikaros nor PAX5β was detected in these cancer cell lines, whereas they could both be amplified from Raji cells. At the protein level, E2A, FOXO1, FOXP1 and NF-κB subunit p65 were all detected in the cancer cells with Western blot assay (Figure 2). Based on the molecular weight, the full length FOXP1 was found to be the main isoform of FOXP1 expressed in the cancer cells. We also confirmed the expression of RAG1 and RAG2 in these cancer cell lines (Figure 2).


Transcription factors E2A, FOXO1 and FOXP1 regulate recombination activating gene expression in cancer cells.

Chen Z, Xiao Y, Zhang J, Li J, Liu Y, Zhao Y, Ma C, Luo J, Qiu Y, Huang G, Korteweg C, Gu J - PLoS ONE (2011)

Gene transcript expression of Ikaros, PAX5β, NF-κB, E2A, FOXO1 and FOXP1 in cancer cell lines.18S was used as an internal control. Raji was used as a positive control. DNase treated RNA without adding reverse transcriptase was used as a negative control.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105062&req=5

pone-0020475-g001: Gene transcript expression of Ikaros, PAX5β, NF-κB, E2A, FOXO1 and FOXP1 in cancer cell lines.18S was used as an internal control. Raji was used as a positive control. DNase treated RNA without adding reverse transcriptase was used as a negative control.
Mentions: RT-PCR results showed that FOXO1, FOXP1, NF-κB subunit p65 and both of the two isoforms of E2A (E47 and E12), were expressed in the cancer cells A549, PC3, MCF-7 and MDA-MB-231 (Figure 1). However, neither Ikaros nor PAX5β was detected in these cancer cell lines, whereas they could both be amplified from Raji cells. At the protein level, E2A, FOXO1, FOXP1 and NF-κB subunit p65 were all detected in the cancer cells with Western blot assay (Figure 2). Based on the molecular weight, the full length FOXP1 was found to be the main isoform of FOXP1 expressed in the cancer cells. We also confirmed the expression of RAG1 and RAG2 in these cancer cell lines (Figure 2).

Bottom Line: It has long been accepted that immunoglobulins (Igs) were produced by B lymphoid cells only.Chromatin immunoprecipitation experiments showed acetylation of RAG enhancer (Erag) and E2A, FOXO1 or FOXP1 were bound to Erag in vivo.These results indicate that in these cancer cells the transcription factors E2A, FOXO1 and FOXP1 regulate RAG expression, which initiates Ig gene rearrangement much in the way similar to B lymphocytes.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Shantou University Medical College, Shantou, China.

ABSTRACT
It has long been accepted that immunoglobulins (Igs) were produced by B lymphoid cells only. Recently Igs have been found to be expressed in various human cancer cells and promote tumor growth. Recombination activating gene 1 (RAG1) and RAG2, which are essential enzymes for initiating variable-diversity-joining segment recombination, have also been found to be expressed in cancer cells. However, the mechanism of RAG activation in these cancer cells has not been elucidated. Here, we investigated the regulatory mechanism of RAG expression in four human cancer cell lines by analyzing transcription factors that induce RAG activation in B cells. By RT-PCR, Western blot and immunofluorescence, we found that transcription factors E2A, FOXO1 and FOXP1 were expressed and localized to the nuclei of these cancer cells. Over-expression of E2A, FOXO1 or Foxp1 increased RAG expression, while RNA interference of E2A, FOXO1 or FOXP1 decreased RAG expression in the cancer cells. Chromatin immunoprecipitation experiments showed acetylation of RAG enhancer (Erag) and E2A, FOXO1 or FOXP1 were bound to Erag in vivo. These results indicate that in these cancer cells the transcription factors E2A, FOXO1 and FOXP1 regulate RAG expression, which initiates Ig gene rearrangement much in the way similar to B lymphocytes.

Show MeSH
Related in: MedlinePlus