Extrapulmonary small cell carcinomas express K homology domain containing protein overexpressed in cancer, but carcinoid tumors do not

Simon, Rebecca; Bourne, Patricia A.; Yang, Qi; Spaulding, Betsy O.; Sant'Agnese, Paul A. di; Wang, Hanlin L.; Xu, Haodong

doi:10.1016/j.humpath.2007.02.001

Cited by 43 publications

(42 citation statements)

References 32 publications

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“…Furthermore, as an RNA-binding protein, it may play a role in the regulation of RNA stability [14][15][16]. In normal mature tissue, its expression is confined to the placenta; however, it is also present in many neoplastic cells including carcinomas of the uterine cervix, endometrium (specifically, endometrial serous carcinoma), ovaries, pancreas, kidneys, stomach, colon, rectum, and lungs (non-small-cell type), as well as some soft tissue sarcomas [16][17][18][19][20][21][22][23][24], but its role in thyroid carcinogenesis and tumor progression is yet to be established. High transcript levels of IMP3 in many different types of cancers suggest that it may play a part in promoting the proliferation of malignant cells [25].…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor mRNA Binding Protein 3 (IMP3) is Differentially Expressed in Benign and Malignant Follicular Patterned Thyroid Tumors

et al. 2009

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Insulin-like growth factor mRNA binding protein 3 (IMP3) is an mRNA-binding protein that regulates transcription of insulin-like growth factor II affecting cell proliferation during embryogenesis. It is highly expressed in carcinomas of the pancreas, stomach, colon, rectum, kidneys, uterine cervix, lung, and ovary. The purpose of our study was to evaluate IMP3 expression in thyroid follicular lesions, to determine whether it has a role in differentiating among these lesions, and to understand their biological relationships. We immunostained 219 thyroid lesions selected from our surgical pathology archives including 14 hyperplastic colloid nodules (CN), 19 Hashimoto's thyroiditis (HT), two Graves disease (GD), ten Hürthle cell adenoma (HCA), 20 follicular adenoma (FA), 37 conventional papillary thyroid carcinoma (PTC), 60 follicular variant of papillary carcinoma (FVPC), 19 Hürthle cell carcinoma (HCC), 32 follicular carcinoma (FC), and six poorly differentiated/anaplastic carcinoma. Immunohistochemistry was performed on formalin-fixed sections using monoclonal antibody to IMP3. Clinicopathological data were also reviewed. In all cases, residual thyroid tissue, CN, HT, GD, HCA, and FA were completely negative for IMP3 staining. Of the 60 FVPC, 23 tumors (38%) were positive for IMP3, with 13 of these (22%) showing very strong staining (3+). Of the 32 FC, 22 tumors (69%) were positive, with seven (22%) showing very strong staining (3+). Furthermore, 33 out of 37 cases (89%) of PTC were negative for IMP3. In all four PTC cases that did stain positive, staining was weak-moderate (1-2+). Similarly, 15 out of 19 cases (79%) of HCC were negative. No significant correlation was found between pathologic tumor characteristics and IMP3 expression in differentiated follicular pattern thyroid carcinoma. With 100% specificity and 69% sensitivity for FC as compared to FA and 100% specificity for FVPC, again compared to FA, IMP3 has the potential to be diagnostically useful in differentiating malignant and benign follicular pattern thyroid lesions. This study also points to a possible common biological relationship between FC and FVPC that requires further investigation.

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Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor mRNA Binding Protein 3 (IMP3) is Differentially Expressed in Benign and Malignant Follicular Patterned Thyroid Tumors

et al. 2009

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“…The total number of IMP-regulated transcripts can be as high as 8,400 in HEK293 cells (12). IMPs are well-characterized markers of various human cancers (13,15,18,34,38), and the molecular mechanisms underlying the function of IMP-1 and IMP-3 have been explored in multiple cancer cell lines (16,23,42). In contrast, next to nothing is known about IMP-2, the most ubiquitously expressed member of the IMP family (13), which is directly regulated by the HMGA2 oncogene in both mouse and human cells (2, 7).…”

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Role of the RNA-Binding Protein IMP-2 in Muscle Cell Motility

Boudoukha

Cuvellier

Polesskaya

2010

Molecular and Cellular Biology

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Insulin-like growth factor 2 (IGF-2) mRNA-binding proteins (IMPs) are a family of posttranscriptional regulatory factors with well-understood roles in embryonic development and cancer but with poorly characterized functions in normal adult cells and tissues. We now show that IMP-2, the most ubiquitously expressed member of the family, is abundant in human and mouse adult skeletal myoblasts, where it is indispensable for cell motility and for stabilization of microtubules. To explore the functions of IMP-2, we analyzed the transcripts that were differentially regulated in IMP-2-depleted myoblasts and bound to IMP-2 in normal myoblasts. Among them were the mRNAs of PINCH-2, an important mediator of cell adhesion and motility, and MURF-3, a microtubule-stabilizing protein. By gain-and loss-of-function assays and gel shift experiments, we show that IMP-2 regulates the expression of PINCH-2 and MURF-3 proteins via direct binding to their mRNAs. Upregulation of PINCH-2 in IMP-2-depleted myoblasts is the key event responsible for their decreased motility. Our data reveal how the posttranscriptional regulation of gene expression by IMP-2 contributes to the control of adhesion structures and stable microtubules and demonstrate an important function for IMP-2 in cellular motility.Terminal differentiation of skeletal muscle leads to irreversible mitotic arrest, accompanied by a decrease in general transcriptional activity. Execution of the myogenic program and maintenance of skeletal muscle tissue depend on various posttranscriptional regulatory mechanisms. We have recently demonstrated how the mRNA-binding protein Lin-28 interacts with translation initiation complexes and enhances the translation of a crucial muscle cytokine, insulin-like growth factor 2 (IGF-2), a function that is indispensable for terminal muscle differentiation (31).Here, we have studied the role of Lin-28 protein partners, the RNA chaperones of the IMP family (IGF-2 mRNA binding proteins), in posttranscriptional regulation of myogenesis. The IMPs (IMP-1, -2, and -3), were first discovered in rhabdomyosarcoma (RMS) cells and were characterized as RNA-binding proteins that share significant structural and functional homology with a number of other RNA-binding posttranscriptional regulators, such as Vg1 RNA binding protein (Vg1RBP), zipcode-binding protein (ZBP), coding region instability determinant binding protein (CRD-BP), and KH-domain-containing protein overexpressed in cancer (KOC) (28, 44). These proteins have been shown to bind to various regions of multiple RNA targets, such as c-myc, ␤-actin, IGF-2, H19, CD44, and many others, and regulate their stability, transport, and/or translation (27,32,36,42). The total number of IMP-regulated transcripts can be as high as 8,400 in HEK293 cells (12). IMPs are well-characterized markers of various human cancers (13,15,18,34,38), and the molecular mechanisms underlying the function of IMP-1 and IMP-3 have been explored in multiple cancer cell lines (16,23,42). In contrast, next to nothing is known about IM...

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“…15 Normal adult tissues that express IMP-3 include term placenta, ovary, testis, brain, lymph node germinal centers, and intestinal mucosa. 13,16,17 Increased levels of IMP-3 have been identified in pancreatic carcinoma, renal cell carcinoma, germ cell neoplasms, ovarian carcinoma, and extrapulmonary small-cell carcinoma, as well as high-grade neuroendocrine carcinoma, squamous cell carcinoma, and adenocarcinoma of the lung. [16][17][18][19][20][21] Additionally, IMP-3 was shown to be a prognostic marker in patients with renal cell carcinoma, with lack of expression in the primary tumor predicting longer metastases-free survival.…”

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IMP-3 is a novel progression marker in malignant melanoma

et al. 2008

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Insulin-like growth factor-II messenger RNA (mRNA)-binding protein-3 (IMP-3), also known as K homology domain-containing protein overexpressed in cancer (KOC) and L523S, is a member of the insulin-like growth factor-II mRNA-binding protein family and is expressed during embryogenesis and in some malignancies. IMP-3 expression in melanocytic neoplasms has not been investigated. Fifty-six melanocytic neoplasms from 48 subjects were immunohistochemically studied using a monoclonal antibody against L523S/IMP-3. IMP-3 expression in melanoma was significantly higher than in Spitz nevi (Po0.05), and the staining intensity in the Spitz nevi was weak. IMP-3 expression in metastatic melanoma was significantly higher than in primary cutaneous melanoma with a Breslow depth r1 mm (Po0.01). None of the benign nevi and dysplastic nevi expressed IMP-3. Our study demonstrates that IMP-3 is expressed in malignant melanoma but not in benign nevi, even when dysplastic features are present; IMP-3 is expressed in a significantly higher proportion of melanomas than Spitz nevi; and IMP-3 is expressed in metastatic melanomas significantly more than in thin melanomas. In conclusion, IMP-3 appears to be involved in the progression of malignant melanoma and may play an important role in the regulation of the biologic behavior of this tumor. Additionally, IMP-3 may have diagnostic utility in distinguishing melanoma from benign nevic cells, dysplastic nevi, and Spitz nevi.

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Extrapulmonary small cell carcinomas express K homology domain containing protein overexpressed in cancer, but carcinoid tumors do not

Cited by 43 publications

References 32 publications

Insulin-Like Growth Factor mRNA Binding Protein 3 (IMP3) is Differentially Expressed in Benign and Malignant Follicular Patterned Thyroid Tumors

Insulin-Like Growth Factor mRNA Binding Protein 3 (IMP3) is Differentially Expressed in Benign and Malignant Follicular Patterned Thyroid Tumors

Role of the RNA-Binding Protein IMP-2 in Muscle Cell Motility

IMP-3 is a novel progression marker in malignant melanoma

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