Vasopressin gene related products are markers of human breast cancer

North, William G.; Pai, Sara I.; Friedmann, Andrew S.; Yu, Xiaoming; Fay, Mike; Memoli, Vincent A.

doi:10.1007/bf00689714

Cited by 30 publications

(22 citation statements)

References 14 publications

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“…In the case of Skbr3 cells, treatment with a combination of dexamethasone, IBMX, and 8br-cAMP enhanced their immunoreactivity with MAG1 mAb. These results are in agreement with earlier findings with H69 SCLC cells, and supported the notion that by inducing an increase in production of proAVP by tumor cells, immuno-based detection and treatment efforts may be enhanced [31]. It is believed that neuropeptides and their receptors can form an autocrine/paracine growth loop in certain tumor cells.…”

Section: Discussionsupporting

confidence: 92%

“…These results are similar to earlier reports that demonstrated proAVP forms of approximately 40, 30, and 20 kDa in SCLC cell lines and tumor extracts [28,29,31]. Mcf7 and Skbr3 cells express a proAVP message that contains a normal sequence, therefore these forms should not be due to an abnormal prohormone.…”

Section: Discussionsupporting

confidence: 91%

“…In both cell lines, a doublet at 38/41 kDa and a band at 20 kDa were detected using the proAVP antibodies ( Figure 2). These results are similar to what we observed in SCLC cell lines and tissue extracts with MAG1 and in breast cancer tissue with NAB1 [28,31]. MAG1 also detected prominent bands at 38 kDa and at 20 kDa in human hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON) tissue extract, while NAB1 detected a single band at 38 kDa.…”

Section: Detection Of Proavp Protein Forms By Western Analysissupporting

confidence: 90%

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Provasopressin expression by breast cancer cells: implications for growth and novel treatment strategies

Keegan

Akerman

Péqueux

et al. 2005

Breast Cancer Res Treat

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SummaryThe arginine vasopressin (AVP) gene is expressed in certain cancers such as breast cancer, where it is believed to act as an autocrine growth factor. However, little is known about the regulation of the AVP protein precursor (proAVP) or AVP-mediated signaling in breast cancer and this study was undertaken to address some of the basic issues. The cultured cell lines examined (Mcf7, Skbr3, BT474, ZR75, Mcf10a) and human breast cancer tissue extract were found to express proAVP mRNA. Western analysis revealed multiple forms of proAVP protein were present in cell lysates, corresponding to those detected in human hypothalamus extracts. Monoclonal antibodies directed against different regions of proAVP bound to intact live Mcf7 and Skbr3 cells. Dexamethasone increased the amount of proAVP-associated glycopeptide (VAG) secreted by Skbr3 cells and a combination of dexamethasone, IBMX and 8br-cAMP increased cellular levels of VAG. Exogenous AVP (1, 10, and 100 nM) elevated phospho-ERK1/2 levels, and increased cell proliferation was observed in the presence of 10 nM AVP. Concurrent treatment with the V1a receptor antagonist SR49059 reduced the effects of AVP on proliferation in Mcf7 cells, and abolished it in Skbr3 cells. Results here show that proAVP components are found at the surface of Skbr3 and Mcf7 cells and are also secreted from these cells. In addition, they show that AVP promotes cancer cell growth, apparently through a Vl-type receptor-mediated pathway and subsequent ERK1/2 activation. Thus, strategies for targeting proAVP should be examined for their effectiveness in diagnosing and treating breast cancer.Keywords : arginine vasopressin (AVP) ; pro-arginine vasopressin (proAVP) ; vasopressin-associated glycopeptide (VAG) ; monoclonal antibody (mAb) ; extracellular signal-regulated kinase (ERK) ; neurophysinrelated surface antigen (NRSA)

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Detection Of Proavp Protein Forms By Western Analysissupporting

confidence: 90%

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Provasopressin expression by breast cancer cells: implications for growth and novel treatment strategies

Keegan

Akerman

Péqueux

et al. 2005

Breast Cancer Res Treat

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“…Rabbit antiserum HenryK was raised against rat neurophysin and displays some cross-reactivity with human neurophysin (23). Rabbit antiserum BorisY2 recognizes the human glycopeptide (24). Rabbit antisera W4 and W1 (25) are raised against vasopressin.…”

Section: Familial Neurohypophysial Diabetes Insipidus (Fndi)mentioning

confidence: 99%

Mutations in the Vasopressin Prohormone Involved in Diabetes Insipidus Impair Endoplasmic Reticulum Export but Not Sorting

Nijenhuis

Zalm

Burbach

1999

Journal of Biological Chemistry

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Familial neurohypophysial diabetes insipidus is characterized by vasopressin deficiency caused by heterozygous expression of a mutated vasopressin prohormone gene. To elucidate the mechanism of this disease, we stably expressed five vasopressin prohormones with a mutation in the neurophysin moiety (NP14G3 R, NP47E3 G, NP47⌬E, NP57G3 S, and NP65G3 V) in the neuroendocrine cell lines Neuro-2A and PC12/PC2. Metabolic labeling demonstrated that processing and secretion of all five mutants was impaired, albeit to different extents (NP65G3 V > NP14G3 R > NP47⌬E > NP47E3 G > NP57G3 S). Persisting endoglycosidase H sensitivity revealed these defects to be due to retention of mutant prohormone in the endoplasmic reticulum. Mutant prohormones that partially passed the endoplasmic reticulum were normally targeted to the regulated secretory pathway. Surprisingly, this also included mutants with mutations in residues involved in binding of vasopressin to neurophysin, a process implicated in targeting of the prohormone. To mimick the high expression in vasopressin-producing neurons, mutant vasopressin prohormones were transiently expressed in Neuro-2A cells. Immunofluorescence displayed formation of large accumulations of mutant prohormone in the endoplasmic reticulum, accompanied by redistribution of an endoplasmic reticulum marker. Our data suggest that prolonged perturbation of the endoplasmic reticulum eventually leads to degeneration of neurons expressing mutant vasopressin prohormones, explaining the dominant nature of the disease.

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“…Expression OF the vasopressin gene appears to be a universal feature of both small-cell lung cancer and breast cancer (Friedmann et al 1994;North et al , 1995North & Yu, 1993a,b). We have now demonstrated this using a combination of immunohistochemistry, Western blot analysis, radioimmunoassay and RT-PCR with sequencing confirmation.…”

Section: Incidence Of Vasopressin Gene Expression By Small-cell Lung mentioning

confidence: 99%

Gene regulation of vasopressin and vasopressin receptors in cancer

North

2000

Experimental Physiology

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It is proposed that neuropeptide production by tumours is an important part of a special process of oncogenic transformation rather than a pre‐existing condition of progenitor cells; this concept is called Selective Tumour gene Expression of Peptides essential for Survival (STEPS). All small‐cell lung cancers and breast cancers evidently express the vasopressin gene, and this gene seems to be structurally normal in all but exceptional cases. Vasopressin gene expression in cancer cells leads to the production of both normal and abnormal forms of tumour vasopressin mRNA and proteins. Although the necessary post‐translational processing enzymes are expressed in these cells, most processing seems to be extragranular, and most of the protein products become components of the plasma membrane. Small‐cell lung cancer and breast cancer cells also express normal genes for all vasopressin receptors and produce normal vasopressin receptor mRNAs and V1a and V1b receptor proteins, and the vasopressin‐activated calcium mobilising (VACM) protein; plus both normal and abnormal forms of the V2 receptor. Through these receptors, vasopressin exercises multifaceted effects on tumour growth and metabolism. A normal protein vasopressin gene promoter seems to be present in small‐cell lung cancer cells, and this promoter contains all of the transcriptional elements known to be involved in gene regulation within hypothalamic neurones. Since these elements largely account for regulation of tumour gene expression observed in vitro, it is likely that as yet unknown factors are selectively produced by tumours in vivo to account for the observed seemingly autonomous or unregulated production of hormone in tumour patients. Promoter elements thought to be responsible for selective vasopressin gene expression in small‐cell lung cancer probably include an E‐box and a neurone restrictive silencer element close to the transcription start site. It is possible that transcription factors acting at these same elements can explain selective vasopressin expression, not only in small‐cell tumours, but also in all other tumours such as breast cancer. By extrapolation, similar mechanisms might also be responsible for the expression of additional features that characterize the ‘neuroendocrine’ profile of these cancers.

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Vasopressin gene related products are markers of human breast cancer

Cited by 30 publications

References 14 publications

Provasopressin expression by breast cancer cells: implications for growth and novel treatment strategies

Provasopressin expression by breast cancer cells: implications for growth and novel treatment strategies

Mutations in the Vasopressin Prohormone Involved in Diabetes Insipidus Impair Endoplasmic Reticulum Export but Not Sorting

Gene regulation of vasopressin and vasopressin receptors in cancer

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