Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular cancer

Hammer, N.A.; Hansen, Thomas V.O.; Byskov, Anne Grete; Meyts, E. Rajpert-De; Grøndahl, Marie Louise; Bredkjær, Helle Ejdrup; Wewer, Ulla M.; Christiansen, Jan; Nielsen, Finn Cilius

doi:10.1530/rep.1.00664

Cited by 129 publications

(128 citation statements)

References 38 publications

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“…7B). As reported previously, all three IMPs are expressed in testes (Hammer et al 2005); however, only IMP2 exhibits broad general expression at a relatively uniform level. The lowest IMP2 expression is seen in the mouse pancreas; however, a preparation of isolated human islets of Langerhans exhibits substantial levels of IMP2 polypeptide, suggesting that IMP expression in the pancreas may be predominantly in islets.…”

Section: Mutation Of Imp2 Ser162 and Ser164 To Ala Inhibits Imp2 Bindsupporting

confidence: 82%

mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry

Dai¹,

Rapley²,

Angel³

et al. 2011

Genes Dev.

166

157

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Variants in the IMP2 (insulin-like growth factor 2 [IGF2] mRNA-binding protein 2) gene are implicated in susceptibility to type 2 diabetes. We describe the ability of mammalian target of rapamycin (mTOR) to regulate the cap-independent translation of IGF2 mRNA through phosphorylation of IMP2, an oncofetal RNA-binding protein. IMP2 is doubly phosphorylated in a rapamycin-inhibitable, amino acid-dependent manner in cells and by mTOR in vitro. Double phosphorylation promotes IMP2 binding to the IGF2 leader 3 mRNA 59 untranslated region, and the translational initiation of this mRNA through eIF-4E-and 59 cap-independent internal ribosomal entry. Unexpectedly, the interaction of IMP2 with mTOR complex 1 occurs through mTOR itself rather than through raptor. Whereas depletion of mTOR strongly inhibits IMP2 phosphorylation in cells, comparable depletion of raptor has no effect; moreover, the ability of mTOR to phosphorylate IMP2 in vitro is unaffected by the elimination of raptor. Dual phosphorylation of IMP2 at the mTOR sites is evident in the mouse embryo, likely coupling nutrient sufficiency to IGF2 expression and fetal growth. Doubly phosphorylated IMP2 is also widely expressed in adult tissues, including islets of Langerhans.

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Section: Mutation Of Imp2 Ser162 and Ser164 To Ala Inhibits Imp2 Bindsupporting

confidence: 82%

mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry

Dai¹,

Rapley²,

Angel³

et al. 2011

Genes Dev.

166

157

View full text Add to dashboard Cite

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“…Other markers, such as Lin28, 60 CD117, 22 and IMP-3, 61 are also expressed in varying percentages in YS(PE)Ts. …”

Section: 15mentioning

confidence: 99%

Germ Cell Tumors of the Ovary: An Update

Nogales

Dulcey

Preda

2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.—The field of ovarian germ cell tumors (OGCTs) has remained relatively unchanged in the last 2 decades. However, the introduction of new stem cell pluripotency markers has provided a new understanding into the identification and taxonomy of OGCT types. New data have provided new insights into unusual teratoma-associated autoimmune disorders and the origin of gliomatosis peritonei. Objective.—To review the impact of new pluripotency markers in the diagnosis of malignant OGCT (MOGCT) and analyze new nomenclature proposals and clinicopathologic entities. Data Sources.—Ovarian germ cell tumors from routine material and expert consultation files at San Cecilio University Hospital, Granada, Spain, and the relevant literature were reviewed. Conclusions.—Although a correct diagnosis of MOGCT can often be made with histologic and classic immunohistochemical studies, the new immunohistochemical pluripotency markers give higher diagnostic accuracy. Germ cell tumors represent a caricature of the phases of normal embryonic differentiation from primordial germ and stem cells to extraembryonal and somatic tissue differentiation. Since every stage of differentiation and its related tumor type exhibit characteristic markers, the analysis of their expression facilitates tumor typing, thus complementing the use of classic antibodies. They also allow a more precise evaluation of the degree of immaturity in teratoma. The new term, primitive endodermal tumors, simplifies the understanding of the complex histology of the yolk sac tumor group, as this terminology encompasses its multiple endodermal differentiations. Recently described autoimmune encephalitis due to antibodies against the N-methyl-d-aspartate receptor has become the most frequent autoimmune disorder associated with ovarian teratoma.

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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.…”

mentioning

confidence: 99%

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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Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular cancer

Cited by 129 publications

References 38 publications

mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry

mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry

Germ Cell Tumors of the Ovary: An Update

IMP-3 is a novel progression marker in malignant melanoma

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