Identification of Annexin VI as a Ca2+-sensitive CRHSP-28-binding Protein in Pancreatic Acinar Cells

Thomas, Diana D. H.; Kaspar, Kala M.; Taft, William B.; Weng, Ning; Rodenkirch, Lance A.; Groblewski, Guy E.

doi:10.1074/jbc.m110917200

Cited by 37 publications

(32 citation statements)

References 40 publications

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“…4). Previously, another member of the TPD52 gene family, the rat CRHSP-28, was studied in the context of gastrointestinal secretion (22). With its gastrointestinal expression and calcium sensitivity, this gene was proposed to be involved in the secretive function of exocrine cells.…”

Section: Discussionmentioning

confidence: 99%

PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression

Wang

Mabjeesh

et al. 2007

Clinical Cancer Research

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Purpose: We previously reported the isolation and characterization of PrLZ, a novel prostatespecific and androgen-responsive gene of the tumor protein D52 family at chromosome 8q21.1. PrLZ is the only known gene in this locus with prostate specificity. Expression level of PrLZ was elevated specifically in cancer cells, suggesting its association with malignancy. Experimental Design:To define its biological function in the morphogenesis, development, and functional maturation of the prostate gland and to gain further insight into its role in prostate cancer, we examined PrLZ expression in prostate specimens during early embryonic development and in adult tissue. Results: PrLZ first appears in the nuclei of the prostate epithelia at 16 weeks of gestation before its distribution in the cytoplasm at later ages. Its expression peaks at 24 years of age, declines at 31years of age, and maintains a minimal level in later age. On prostate cancer development, PrLZ expression is reactivated, and its expression increases from primary localized tumor to bone metastasis. Overexpression of PrLZ in prostate cancer cells accelerates their growth in vitro and tumor formation in vivo. Conclusion: This work identifies PrLZ as a marker for prostate cancer progression and metastasis, andits pattern of expression is suggestive of a proto-oncogene.

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Section: Discussionmentioning

confidence: 99%

PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression

Wang

Mabjeesh

et al. 2007

Clinical Cancer Research

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“…For cryostat sections of rat pancreas (Figs. 2 and 4A), lobules were fixed in 4% paraformaldehyde, and immunofluorescence microscopy was conducted on 9-m-thick cryostat sections as previously described (22,23). For images of acinar cell whole mounts (Fig.…”

Section: Methodsmentioning

confidence: 99%

Pancreatic Acinar Cells Express Vesicle-associated Membrane Protein 2- and 8-Specific Populations of Zymogen Granules with Distinct and Overlapping Roles in Secretion

Weng¹,

Thomas²,

Groblewski

2007

Journal of Biological Chemistry

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Previous studies have demonstrated roles for vesicle-associated membrane protein 2 (VAMP 2) and VAMP 8 in Ca 2؉ -regulated pancreatic acinar cell secretion, however, their coordinated function in the secretory pathway has not been addressed. Here we provide evidence using immunofluorescence microscopy, cell fractionation, and SNARE protein interaction studies that acinar cells contain two distinct populations of zymogen granules (ZGs) expressing either VAMP 2 or VAMP 8. Further, VAMP 8-positive granules also contain the synaptosome-associated protein 29, whereas VAMP 2-expressing granules do not. Analysis of acinar secretion by Texas red-dextran labeling indicated that VAMP 2-positive ZGs mediate the majority of exocytotic events during constitutive secretion and also participate in Ca 2؉ -regulated exocytosis, whereas VAMP 8-positive ZGs are more largely involved in Ca 2؉ -stimulated secretion. Previously undefined functional roles for VAMP and syntaxin isoforms in acinar secretion were established by introducing truncated constructs of these proteins into permeabilized acini. VAMP 2 and VAMP 8 constructs each attenuated Ca 2؉ -stimulated exocytosis by 50%, whereas the neuronal VAMP 1 had no effects. In comparison, the plasma membrane SNAREs syntaxin 2 and syntaxin 4 each inhibited basal exocytosis, but only syntaxin 4 significantly inhibited Ca 2؉ -stimulated secretion. Syntaxin 3, which is expressed on ZGs, had no effects. Collectively, these data demonstrate that individual acinar cells express VAMP 2-and VAMP 8-specific populations of ZGs that orchestrate the constitutive and Ca 2؉ -regulated secretory pathways.The exocrine pancreas is responsible for synthesizing and secreting a variety of digestive enzymes that are essential for assimilation of the diet. Secretion occurs by exocytosis of large dense core zymogen granules (ZGs) 3 localized in the apical cytoplasm of acinar cells. Similar to endocrine and neural cells, exocytosis is highly induced following acinar stimulation by secretagogues; however, acini are unique in that a significant proportion of exocytosis also occurs by a constitutive pathway under basal conditions. Secretagogue-stimulated exocytosis is mediated by G protein-coupled receptors, which signal through phospholipase C and/or adenylate cyclase, and The process of exocytosis and other membrane fusion events is widely held to be regulated by soluble N-ethylmaleimidesensitive factor attachment protein receptor (SNARE) interactions in cells (3-5). SNARE proteins are classified as either Q-SNARE or R-SNARE based on conserved glutamine (Q) and arginine (R) residues positioned within their characteristic coiled-coil motifs. When brought in close opposition, Q-and R-SNAREs on each membrane form a heterotrimeric complex that provides the driving force for membrane fusion. In neurons, one R-containing coil of the complex is derived from vesicle-associated membrane protein (VAMP/synaptobrevin) present on synaptic vesicles, and one Q-containing coil is contributed by syntaxin 1 located on the pre...

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“…A critical chromosome 8q21.13 gene is indicated to be tumor protein D52 (TPD52 or D52; refs. 6 -9), a member of the D52-like family of adaptor proteins (10,11). Human D52 transcripts or protein are overexpressed in breast, prostate, and ovarian cancer, with this being associated with increased gene copy number in a proportion of cases (6 -9).…”

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confidence: 99%

Nonredundant Functions for Tumor Protein D52-Like Proteins Support Specific Targeting of TPD52

Shehata

Bièche

Boutros

et al. 2008

Clinical Cancer Research

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Purpose: Tumor protein D52 (TPD52 or D52) is frequently overexpressed in breast and other cancers and present at increased gene copy number. It is, however, unclear whether D52 amplification and overexpression target specific functional properties of the encoded protein.Experimental Design: The expression of D52-like genes and MAL2 was compared in breast tissues using quantitative reverse transcription-PCR.The functions of human D52 and D53 genes were then compared by stable expression in BALB/c 3T3 fibroblasts and transient gene knockdown in breast carcinoma cell lines. In situ D52 and MAL2 protein expression was analyzed in breast tissue samples using tissue microarray sections. Results: The D52 (8q21.13), D54 (20q13.33), and MAL2 (8q24.12) genes were significantly overexpressed in breast cancer tissue (n = 95) relative to normal breast (n = 7; P V 0.005) unlike the D53 gene (6q22.31; P = 0.884). Subsequently, D52-expressing but not D53-expressing 3T3 cell lines showed increased proliferation and anchorage-independent growth capacity, and reduced D52 but not D53 expression in SK-BR-3 cells significantly increased apoptosis. High D52 but not MAL2 expression was significantly associated with reduced overall survival in breast carcinoma patients (log-rank test, P < 0.001; n = 357) and was an independent predictor of survival (hazard ratio, 2.274; 95% confidence interval, 1.228-4.210; P = 0.009; n = 328). Conclusion: D52 overexpression in cancer reflects specific targeting and may contribute to a more proliferative, aggressive tumor phenotype in breast cancer.

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Identification of Annexin VI as a Ca2+-sensitive CRHSP-28-binding Protein in Pancreatic Acinar Cells

Cited by 37 publications

References 40 publications

PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression

PrLZ Is Expressed in Normal Prostate Development and in Human Prostate Cancer Progression

Pancreatic Acinar Cells Express Vesicle-associated Membrane Protein 2- and 8-Specific Populations of Zymogen Granules with Distinct and Overlapping Roles in Secretion

Nonredundant Functions for Tumor Protein D52-Like Proteins Support Specific Targeting of TPD52

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