Antipeptide antibodies against the pNR‐2 oestrogen‐regulated protein of human breast cancer cells and detection of pNR‐2 expression in normal tissues by immunohistochemistry

Piggott, Nigel H.; Henry, James A.; May, Felicity E. B.; Westley, Bruce R.

doi:10.1002/path.1711630204

Cited by 76 publications

(46 citation statements)

References 19 publications

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“…It belongs to the trefoil factor family of proteins, is expressed predominately in gastric mucosa, and is synthesized by mucosal epithelial cells (42,43). It has antiapoptotic and motogenic activities, and its main functions …”

Section: Discussionmentioning

confidence: 99%

Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor

Chutipongtanate

Nakagawa²,

Sritippayawan³

et al. 2005

Journal of Clinical Investigation

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Previous research on proteins that inhibit kidney stone formation has identified a relatively small number of well-characterized inhibitors. Identification of additional stone inhibitors would increase understanding of the pathogenesis and pathophysiology of nephrolithiasis. We have combined conventional biochemical methods with recent advances in mass spectrometry (MS) to identify a novel calcium oxalate (CaOx) crystal growth inhibitor in normal human urine. Anionic proteins were isolated by DEAE adsorption and separated by HiLoad 16/60 Superdex 75 gel filtration. A fraction with potent inhibitory activity against CaOx crystal growth was isolated and purified by anion exchange chromatography. The protein in 2 subfractions that retained inhibitory activity was identified by matrix-assisted laser desorption/ionization-time-of-flight MS and electrospray ionization-quadrupole-time-of-flight tandem MS as human trefoil factor 1 (TFF1). Western blot analysis confirmed the mass spectrometric protein identification. Functional studies of urinary TFF1 demonstrated that its inhibitory potency was similar to that of nephrocalcin. The inhibitory activity of urinary TFF1 was dose dependent and was inhibited by TFF1 antisera. Anti-C-terminal antibody was particularly effective, consistent with our proposed model in which the 4 C-terminal glutamic residues of TFF1 interact with calcium ions to prevent CaOx crystal growth. Concentrations and relative amounts of TFF1 in the urine of patients with idiopathic CaOx kidney stone were significantly less (2.5-fold for the concentrations and 5-to 22-fold for the relative amounts) than those found in controls. These data indicate that TFF1 is a novel potent CaOx crystal growth inhibitor with a potential pathophysiological role in nephrolithiasis.

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Section: Discussionmentioning

confidence: 99%

Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor

Chutipongtanate

Nakagawa²,

Sritippayawan³

et al. 2005

Journal of Clinical Investigation

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“…Three members of this family have been identified in humans consisting of one (pS2 and ITF) or two (SP) trefoil domains. pS2 was originally identified through its apparent ectopic expression in human breast carcinomas (10), although it has subsequently been shown that the normal breast also produces pS2 (13). Trefoil peptides are also expressed in the normal gastrointestinal tract in a site specific fashion; pS2 and SP are expressed predominantly in the stomach mucosa, whereas ITF is produced by the goblet cells of the colon.…”

Section: Discussionmentioning

confidence: 99%

Transgenic mice that overexpress the human trefoil peptide pS2 have an increased resistance to intestinal damage.

Marchbank

Goodlad

Chinery

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

168

123

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ABSTRACTpS2 is a member of the trefoil peptide family, all of which are overexpressed at sites of gastrointestinal injury. We hypothesized that they are important in stimulating mucosal repair. To test this idea, we have produced a transgenic mice strain that expresses human pS2 (hpS2) specifically within the jejunum and examined the effect of this overexpression on proliferation and susceptibility to indomethacin-induced damage. A transgenic mouse was produced by microinjecting fertilized oocytes with a 1.7-kb construct consisting of rat intestinal fatty acid binding protein promoter (positions -1178 to +28) linked to full-length (490 bp) hpS2 cDNA. Screening for positive animals was by Southern blot analysis. Distribution of hpS2 expression was determined by using Northern and Western blot analyses and immunohistochemical staining. Proliferation of the intestinal mucosa was determined by assessing the crypt cell production rate. Differences in susceptibility to intestinal damage were analyzed in animals that had received indomethacin (85 mg/kg s.c.) 0-30 h previously. Expression of hpS2 was limited to the enterocytes of the villi within the jejunum. In the nondamaged intestine, villus height and crypt cell production rate were similar in transgenic and negative (control) litter mates. However, there was a marked difference in the amount of damage caused by indomethacin in control and transgenic animals in the jejunum (30% reduction in villus height in controls vs. 12% reduction in transgenic animals, P < 0.01) but the damage sustained in the non-hpS2-expressing ileal region was similar in control and transgenic animals. These studies support the hypothesis that trefoil peptides are important in stimulating gastrointestinal repair.

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“…A large number of studies indicate that TFF1 expression is absent or occurs at low levels in nonmalignant pancreatic and prostate tissues. Elevated expression levels of TFF1 are frequently observed in pancreatic and prostate malignancies (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31), suggesting that TFF1 may be involved in the tumorigenesis of these cancers. These data are not, however, sufficiently convincing because of the lack of strict statistical analysis in some studies and the reduced statistical power in others with small sample sizes.…”

Section: Tff1 Expressionmentioning

confidence: 99%

Trefoil factor 1 acts to suppress senescence induced by oncogene activation during the cellular transformation process

Radiloff

Wakeman²,

Feng³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Senescence is a cellular stress response characterized by persistent cell growth arrest under various stress conditions, including oncogene activation or tumor suppressor loss, which functions as a critical barrier that must be overcome to allow the progression from a precancerous or preinvasive lesion to a malignant tumor. Trefoil factor 1 (TFF1) is a secreted protein involved in maintaining the gastrointestinal epithelium by serving a tumor-suppressive role; however, TFF1 is overexpressed in several types of cancers. Here we report that TFF1 acts as a promoter of tumorigenesis in the context of prostate and pancreatic cancers by suppressing oncogene-induced senescence (OIS). Expression of TFF1 allows human prostate epithelial cells to escape OIS caused by the activated Ras oncogene or by reduced expression of the tumor suppressor PTEN, in part by the involvement of the EGF receptor-mediated pathway and inhibition of the expression of the cell cycle regulator p21. Without intrinsic promitogenic activity TFF1 may act in both autocrine and paracrine manners to enable cells to undergo the initial transformation and expansion against the restrictive microenvironment during early stage tumorigenesis. Taken together, our findings identify TFF1 as a soluble factor designed to act mainly to antagonize the OIS process to accelerate tumorigenesis.

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Antipeptide antibodies against the pNR‐2 oestrogen‐regulated protein of human breast cancer cells and detection of pNR‐2 expression in normal tissues by immunohistochemistry

Cited by 76 publications

References 19 publications

Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor

Identification of human urinary trefoil factor 1 as a novel calcium oxalate crystal growth inhibitor

Transgenic mice that overexpress the human trefoil peptide pS2 have an increased resistance to intestinal damage.

Trefoil factor 1 acts to suppress senescence induced by oncogene activation during the cellular transformation process

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