Characterization of the human polymeric immunoglobulin receptor(PIGR) 3'UTR and differential expression ofPIGR mRNA during colon tumorigenesis

Traicoff, June L.; Marchis, Laura De; Ginsburg, Britten L.; Zamora, Rodolfo E.; Khattar, Nada H.; Blanch, Vincent J.; Plummer, Sarah J.; Bargo, Sharon; Templeton, Dennis J.; Casey, Graham; Kaetzel, Charlotte S.

doi:10.1007/bf02256332

Cited by 9 publications

(17 citation statements)

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“…Traicoff et al recently reported differential expression of PIGR mRNA during colon carcinogenesis, which may be due to both transcriptional and post-transcriptional mechanisms [39]. An 'E-Box' motif in the promoter of the human PIGR gene has been shown to be essential for basal transcription in colon carcinoma cell-lines [10,40,41].…”

Section: Discussionmentioning

confidence: 98%

“…We have recently sequenced the 3¢UTR of the human PIGR gene, and have identified potential binding sites for proteins that may affect the stability of PIGR mRNA [39]. It is possible that dysregulation of USF and/or AP2-a expression could reduce stability of PIGR mRNA indirectly by altering transcription of genes encoding mRNA regulatory proteins.…”

Section: Discussionmentioning

confidence: 99%

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Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung carcinoma: correlation with dysregulated expression of the transcription factors USF and AP2

2005

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The polymeric immunoglobulin receptor (PIGR) mediates transport of IgA and IgM antibodies across mucosal and glandular epithelia. Several studies have utilized immunohistochemistry to demonstrate that PIGR expression varies in different types of lung carcinoma, and is down-regulated during tumor progression. We have previously shown in cultured tumor cell-lines that basal transcription of the PIGR gene is regulated by the transcription factors USF1, USF2 and AP2. To examine the mechanism by which PIGR expression is down-regulated in lung carcinoma, RNA was microdissected from formalin-fixed, paraffin-embedded lung carcinomas (14 adenocarcinomas and 8 squamous cell carcinomas). Levels of PIGR, USF1, USF2 and AP2-alpha mRNA were quantified by real-time reverse transcriptase-polymerase chain reaction and normalized to mRNA for the housekeeping gene GAPDH. PIGR mRNA levels were decreased in adenocarcinomas and squamous cell carcinomas relative to adjacent non-tumor tissue, and were inversely correlated with stage of differentiation. USF1 and USF2 mRNA levels were reduced in adenocarcinomas relative to non-tumor tissue, while AP2-alpha levels were elevated. Multivariate regression analysis demonstrated that reduced USF2 mRNA and increased AP2-alpha mRNA levels were predictive of down-regulated PIGR mRNA expression in the majority of adenocarcinomas and in moderately differentiated squamous cell carcinomas.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung carcinoma: correlation with dysregulated expression of the transcription factors USF and AP2

2005

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“…Downregulation of pIgR expression is a common feature of adenocarcinomas originating from mucosal tissues, including the colon (Poger et al, 1976;Rognum et al, 1980Rognum et al, , 1982Isaacson, 1982b;Arends et al, 1984;Wiggers et al, 1988;Koretz et al, 1994;Krajci et al, 1996;Traicoff et al, 2003), esophagus (Gologan et al, 2008), and lung (Harris and South, 1981;Brooks and Ernst, 1984;Espinoza et al, 1984;Loosli and Hurlimann, 1984;Kodama et al, 1985;Kondi-Paphitis and Addis, 1986;Popper et al, 1987;Kawai et al, 1988;Ordonez, 1989;Hirata et al, 1990;Ishida et al, 1990a,b;Brown et al, 1993;Khattar et al, 2005;Ocak et al, 2012). Two studies using microarray analysis to identify gene expression biomarkers for colorectal cancer reported that decreased pIgR mRNA levels in metastatic tumors (Jorissen et al, 2009) and colonic biopsies (Agesen et al, 2012) were associated with poor prognosis.…”

Section: Dysregulation Of Pigr Expression In Disease Statesmentioning

confidence: 98%

Immunoglobulin Transport and Immunoglobulin Receptors

2015

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“…In addition, posttranscriptional modulation also contributes to pIgR induction by proinflammatory cytokines (17). Chronic proinflammatory stimulation, or oncogenic insults, cause a marked increase in pIgR mRNA stability, mechanistically acting on the 1.8-kb 39-untranslated region (39-UTR) of human pIgR mRNA that contains multiple repetitive elements important for the processing and stability of pIgR transcripts (18). In particular, adenylate-uridylate-rich elements (AREs) located in the 39-UTR of unstable genes mediate selective mRNA stabilization in response to diverse intra-and extracellular signaling molecules (19).…”

mentioning

confidence: 99%

Ribosome Inactivation Leads to Attenuation of Intestinal Polymeric Ig Receptor Expression via Differential Regulation of Human Antigen R

Hun

Park

Kim

et al. 2016

The Journal of Immunology

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The polymeric IgR (pIgR) is a central component in the transport of IgA across enterocytes and thereby plays a crucial role in the defense against enteropathogens and in the regulation of circulating IgA levels. The present study was performed to address the novel regulation of pIgR expression in intestinal epithelia undergoing ribosome inactivation. Insults to mucosa that led to ribosome inactivation attenuated pIgR expression in enterocytes. However, IFN regulatory factor-1 (IRF-1) as a central transcription factor of pIgR induction was superinduced by ribosome inactivation in the presence of IFN-γ as a result of mRNA stabilization by the RNA-binding protein HuR. Another important transcription factor for pIgR expression, NF-κB, was marginally involved in suppression of pIgR by ribosome inactivation. In contrast to a positive contribution of HuR in early induction of IRF-1 expression, extended exposure to ribosome inactivation caused nuclear entrapment of HuR, resulting in destabilization of late-phase–induced pIgR mRNA. These HuR-linked differential regulations of pIgR and of IRF-1 led to a reduced mucosal secretion of IgA and, paradoxically, an induction of IRF-1–activated target genes, including colitis-associated IL-7. Therefore, these events can account for ribosome inactivation–related mucosal disorders and provide new insight into interventions for HuR-linked pathogenesis in diverse mucosa-associated diseases, including inflammatory bowel disease and IgA nephritis.

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Characterization of the human polymeric immunoglobulin receptor(PIGR) 3'UTR and differential expression ofPIGR mRNA during colon tumorigenesis

Cited by 9 publications

References 48 publications

Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung carcinoma: correlation with dysregulated expression of the transcription factors USF and AP2

Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung carcinoma: correlation with dysregulated expression of the transcription factors USF and AP2

Immunoglobulin Transport and Immunoglobulin Receptors

Ribosome Inactivation Leads to Attenuation of Intestinal Polymeric Ig Receptor Expression via Differential Regulation of Human Antigen R

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