Two-dimensional gel electrophoresis analyses identify nucleophosmin as an estrogen regulated protein associated with acquired estrogen-independence in human breast cancer cells

Skaar, Todd C.; Prasad, Sarada C.; Sharareh, Sheri; Lippman, Marc E.; Brünner, Nils; Clarke, Robert

doi:10.1016/s0960-0760(98)00142-3

Cited by 57 publications

(49 citation statements)

References 44 publications

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“…In agreement with these observations, NPM1 was among genes whose transcription was regulated by estrogen in breast cancer cells. 41,42 In the present study, our in vitro results confirm the up-regulation of NPM protein by estrogen treatment in ER ϩ breast cancer cells. We also found that increased NPM expression induced either by estrogen or lentiviruses affected NPM subcellular localization.…”

Section: Discussionsupporting

confidence: 85%

An Extensive Tumor Array Analysis Supports Tumor Suppressive Role for Nucleophosmin in Breast Cancer

Karhemo

Rivinoja

Lundin

et al. 2011

The American Journal of Pathology

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Nucleophosmin (NPM) is a multifunctional protein involved in a complex network of interactions. The role of NPM in oncogenesis is controversial. The NPM gene (NPM1) is mutated or rearranged in a number of hematological disorders, but such changes have not been detected in solid cancers. However, experiments with cultured NPM-null cells and with mice carrying a single inactivated NPM allele indicate a tumor suppressor function for NPM. To resolve the role of NPM in solid cancers, we examined its expression and localization in histologically normal breast tissue and a large array of human breast carcinoma samples (n ‫؍‬ 1160), and also evaluated its association with clinicopathological variables and patient survival. The intensity and localization (nucleolar, nuclear, cytoplasmic) of NPM varied across clinical samples. No mutations explaining the differences were found, but the present findings indicate that expression levels of NPM affected its localization. Our study also revealed a novel granular staining pattern for NPM, which was an independent prognostic factor of poor prognosis. In addition, reduced levels of NPM protein were associated with poor prognosis. Nucleophosmin (NPM) is a ubiquitously expressed multifunctional nucleolar phosphoprotein. It localizes mainly to the nucleoli, but also shuttles in and out of the nucleolus, and between the nucleus and the cytoplasm. 1,2 NPM belongs to the nucleoplasmin family of nuclear chaperone proteins. It is involved in a complex network of interactions and has multiple functions. In addition to its chaperone activity, 3,4 NPM is involved in centrosome duplication, 5 ribosome biogenesis, 6,7 and environmental stress responses. 8,9 NPM also regulates the tumor suppressor proteins p53 10 -12 and p14 ARF . [13][14][15] Moreover, NPM protein is post-translationally modified by acetylation, 16 sumoylation, 17,18 ubiquitinylation, 19 and phosphorylation. 20 -23 NPM has been heavily implicated in cancer pathogenesis, but its actual role in oncogenesis is controversial. 24 NPM1 is mutated or rearranged in a number of hematological disorders, 25 and it is the most frequently mutated gene in acute myeloid leukemia. In addition, NPM protein is reported to be overexpressed in cancer cells, and it was originally proposed as a proto-oncogene. However, rapidly proliferating tumor cells could show elevated NPM levels, simply because NPM expression increases rapidly in early G1 phase during mitosis. 26 On the other hand, inactivation of NPM1 in the germline leads to embryonic lethality. 27,28 Moreover, experiments with cultured NPM-null cells 27,28 and mice carrying a single inactivated NPM allele indicate a tumor suppressor function for NPM. 27 NPM1

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Section: Discussionsupporting

confidence: 85%

An Extensive Tumor Array Analysis Supports Tumor Suppressive Role for Nucleophosmin in Breast Cancer

Karhemo

Rivinoja

Lundin

et al. 2011

The American Journal of Pathology

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“…Not previously reported in breast cancer cells, we now have preliminary data to suggest that this functional interaction also occurs in T47D cells (not shown). NPM is an estrogen-induced protein in MCF-7 cells that is down-regulated by antiestrogens (66), and its expression is increased in MCF-7/LCC9 when compared with MCF-7/LCC1 cells (19). Thus, in addition to down-regulating IRF-1 mRNA expression, antiestrogen-resistant cells have up-regulated expression of an endogenous inhibitor (NPM).…”

Section: Discussionmentioning

confidence: 99%

Interferon Regulatory Factor-1 Mediates the Proapoptotic but Not Cell Cycle Arrest Effects of the Steroidal Antiestrogen ICI 182,780 (Faslodex, Fulvestrant)

et al. 2004

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“…We observed upregulation of the expression of a set of genes involved in cell proliferation that have, to our knowledge, not been previously studied in heart. First, NPM, which is known to accumulate in nuclei of exponentially growing HeLa cells (55) and is strongly upregulated during estrogen-induced cell proliferation in MCF-7 breast cancer cells (50), was continuously upregulated after 10 wk of HFD. NPM has several potentially important roles in regulating cell function and signaling.…”

Section: Discussionmentioning

confidence: 99%

Kinetic analysis of cardiac transcriptome regulation during chronic high-fat diet in dogs

Philip-Couderc

Smih

Hall

et al. 2004

Physiological Genomics

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Rouet. Kinetic analysis of cardiac transcriptome regulation during chronic high-fat diet in dogs. Physiol Genomics 19: 32-40, 2004. First published June 29, 2004 doi:10.1152/physiolgenomics.00001.2004In the present study, we investigated, using custom dog cDNA arrays, the time course of transcriptional changes in the left ventricle of dogs fed a normal diet or a high-fat diet (HFD) for 9-24 wk. Array hybridizations were performed with complex probes representing mRNAs expressed in left ventricles from obese hypertensive and lean control dogs. We identified 63 differentially expressed genes, and expression of 17 of 20 randomly chosen genes was confirmed by real-time PCR. Transcripts were categorized into groups involved in metabolism, cell signaling, tissue remodeling, ionic regulation, cell proliferation, and protein synthesis. Hierarchical clustering indicated that the pattern of coregulated genes depends on duration of the HFD, suggesting that HFD-induced obesity hypertension is associated with continuous cardiac transcriptome adaptation despite stability of both body weight and blood pressure. GenMAPP analysis of the data pointed out the crucial importance of the ventricle TGF-␤ pathway. Our results suggest that this system may be involved in molecular remodeling during HFD and in changes observed in the transcription profile, reflecting functional and morphological abnormalities that arise during prolonged HFD. These results also suggest some novel regulatory pathways for cardiac adaptation to obesity. hypertension; obesity; functional genomics; hypertension; arrays; heart OBESITY IS HIGHLY PREVALENT in developed countries and will be a major health concern in the future mainly because of its impact on cardiovascular morbidity and mortality (22,27,35,49). Duration of obesity has been shown to be a determinant of the incidence and severity of obesity-associated cardiac morbidity (4, 36), raising the probability that the recent increase in prevalence of childhood obesity will in the future result in a marked rise in the appearance of cardiovascular diseases (14,34,44). Cardiovascular morbidity in obesity is, in part, a consequence of arterial hypertension (33) as well as endocrine and metabolic disorders such as insulin resistance, diabetes mellitus, or dyslipidemia. However, increased adiposity enhances secretion of multiple adipokines (53) that may act on target organs such as kidney, brain, and heart (19).Our group and others have investigated the cardiovascular adaptations to obesity in dogs fed a hyperlipidic, hypercaloric diet (HFD) (17,43,54). This model closely mimics human obesity and is associated with hypertension, cardiac dysfunction, and metabolic abnormalities. This is in contrast to many mouse and rat genetic models of obesity with defects in leptin synthesis or leptin signaling. In most of these models obesity is not associated with sympathetic nervous system activation or hypertension. Moreover, dietary models of obesity, especially those produced by feeding an HFD, mimic the diet of Western ...

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Two-dimensional gel electrophoresis analyses identify nucleophosmin as an estrogen regulated protein associated with acquired estrogen-independence in human breast cancer cells

Cited by 57 publications

References 44 publications

An Extensive Tumor Array Analysis Supports Tumor Suppressive Role for Nucleophosmin in Breast Cancer

An Extensive Tumor Array Analysis Supports Tumor Suppressive Role for Nucleophosmin in Breast Cancer

Interferon Regulatory Factor-1 Mediates the Proapoptotic but Not Cell Cycle Arrest Effects of the Steroidal Antiestrogen ICI 182,780 (Faslodex, Fulvestrant)

Kinetic analysis of cardiac transcriptome regulation during chronic high-fat diet in dogs

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