Absence of RBM expression as a marker of intratubular (in situ) germ cell neoplasia of the testis

Lifschitz-Mercer, Beatriz; Elliott, David J.; Leider-Trejo, Leonor; Schreiber-Bramante, Letizia; Hassner, Avi; Eisenthal, Avi; Maymon, Batia Bar-Shira

doi:10.1053/hupa.2000.16671

Cited by 23 publications

(17 citation statements)

References 24 publications

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“…RBM8A and RBM8B interact with the tumor suppressor gene OVCA1, 32 and RBMY is downregulated during testicular cancer progression. 33,34 Additional studies on well-annotated tumor samples are warranted to confirm the utility of RBM3 as a prognostic biomarker in various cancer forms.…”

Section: Discussionmentioning

confidence: 99%

Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer

et al. 2009

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Single-strand RNA-binding proteins (RBPs) are involved in many aspects of RNA metabolism and in the regulation of gene transcription. The RBP RBM3 was recently suggested to be a proto-oncogene in colorectal cancer; however, such a role has not been corroborated by previous studies in the colon or other tumor types, and the prognostic implications of tumor-specific RBM3 expression remain unclear. Mono-specific antibodies against RBM3 were generated. Antibody specificity was confirmed using siRNA gene silencing, western blotting and immunohistochemistry on a panel of breast cancer cell lines. Using tissue microarrays and IHC, RBM3 protein expression was examined in 48 normal tissues and in 20 common cancers. Additional analysis in two independent breast cancer cohorts (n ¼ 1016) with long-term follow-up was also carried out. RBM3 was upregulated in cancer compared to normal tissues. The nuclear expression of RBM3 in breast cancer was associated with low grade (Po0.001), small tumors (Po0.001), estrogen receptor (ER) positivity (Po0.001) and Ki-67 negativity (Po0.001) in both the breast cancer cohorts. An increased nuclear expression of RBM3 was associated with a prolonged overall and recurrence-free survival. The prognostic value was particularly pronounced in hormone receptor-positive tumors and remained significant in multivariate interaction analysis after controlling for tamoxifen treatment (HR: 0.49, 95% CI: 0.30-0.79, P ¼ 0.004). These data strongly indicate that nuclear RBM3 is an independent favorable prognostic factor in breast cancer, and seems to have a specific role in ER-positive tumors.

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Section: Discussionmentioning

confidence: 99%

Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer

et al. 2009

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“…Although sequential expression of various genes in adipocyte differentiation has been extensively investigated (30,31), there is no report on the differentiation-dependent expression pattern of these serine/threonine phosphatases. An earlier study reported that PP2C␣ is expressed in various human tissues (32), but PP2C␣ has not been examined in adipose tissue. Thus, we first demonstrated the possible importance of PP2C␣ in the acquisition by adipocytes of insulin sensitivity during the differentiation process.…”

Section: Discussionmentioning

confidence: 99%

Protein Phosphatase-2Cα as a Positive Regulator of Insulin Sensitivity through Direct Activation of Phosphatidylinositol 3-Kinase in 3T3-L1 Adipocytes

Yoshizaki

Maegawa

Egawa

et al. 2004

Journal of Biological Chemistry

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During differentiation, expression of protein phosphatase-2C␣ (PP2C␣) is increased in 3T3-L1 adipocytes.To elucidate the role of PP2C␣ in insulin signaling, we overexpressed wild-type (WT) PP2C␣ by adenovirus-mediated gene transfer in 3T3-L1 adipocytes. Overexpression of PP2C␣-WT enhanced the insulin sensitivity of glucose uptake without any changes in the early steps of insulin signaling. Infection with adenovirus 5 expressing PP2C␣-WT increased phosphatidylinositol 3-kinase (PI3K) activities in the immunoprecipitate using antibody against the p85 or p110 subunit under both basal and insulin-stimulated conditions, followed by activation of downstream steps in the PI3K pathway, such as phosphorylation of Akt, glycogen synthase kinase-3, and atypical protein kinase C. In contrast, overexpression of the phosphatase-defective mutant PP2C␣(R174G) did not produce such effects. Furthermore, overexpression of PP2C␣-WT (but not PP2C␣(R174G)) decreased the 32 P-labeled phosphorylation state as well as the gel mobility shift of the p85 subunit, suggesting that dephosphorylation of the p85 subunit by PP2C␣ activation might stimulate PI3K catalytic activity. Moreover, knockdown of PP2C␣ by transfection of small interfering RNA led to a significant decrease in Akt phosphorylation. In addition, microinjection of anti-PP2C␣ antibody or PP2C␣ small interfering RNA led to decreased insulin-stimulated GLUT4 translocation. In conclusion, PP2C␣ is a new positive regulator of insulin sensitivity that acts through a direct activation of PI3K in 3T3-L1 adipocytes.Phosphorylation state is regulated by both protein kinase and protein phosphatase and is critical for the regulation of cellular functions such as cell growth, differentiation, and metabolism (1, 2). The protein phosphatases of eukaryotic cells are structurally and functionally diverse enzymes that can be divided into two distinct families (serine/threonine phosphatases and protein-tyrosine phosphatases) based on their specificities for phosphoamino acids (3, 4). Serine/threonine phosphatases are further classified into four major groups (protein phosphatase (PP) 1 -1, PP2A, PP2B, and PP2C␣) depending on their substrate specificities, bivalent cation dependences, and sensitivities to various inhibitor molecules such as protein inhibitor-1 and -2 and the tumor promoter okadaic acid (3, 5).The role of protein-tyrosine phosphatases in insulin signaling has been well characterized in several recent studies (6 -11). As does tyrosine phosphorylation, serine/threonine phosphorylation plays important roles in insulin signal transduction. A major role in the negative regulation of insulin action is attributed to agents that enhance serine/threonine phosphorylation of the receptor itself or its downstream effectors such as insulin receptor substrate-1 (IRS-1). Serine/threonine phosphorylation of such molecules induces insulin resistance. Furthermore, Akt and atypical protein kinase C (PKC ) are serine/threonine kinases, and their kinase activities are regulated through the serine/threo...

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“…Sections were counterstained with Mayer's hematoxylin which stains the nuclei blue in color germ cell marker, DAZL1, in the putative ontogenic progenitor, IGCN, and in the putative derivative, seminoma, provides further support for the hypothesis that IGCN is the precursor of germ cell neoplasia. Much effort has been expended in studying the origin and differentiation patterns of germ cell neoplasias using morphological, immunohistochemical; and genetic criteria [1,5,10,11,30]. Based on the model of a germ cell tumor's histogenesis [25], it is widely accepted that all forms of testicular germ cell tumors -with the notable exception of spermatocytic seminoma -are derived from a common precursor, originally recognized and described as IGCN and also designated as carcinoma in situ of the testis [23].…”

Section: Discussionmentioning

confidence: 99%

Localization of a specific germ cell marker, DAZL1, in testicular germ cell neoplasias

et al. 2001

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DAZ-like 1( DAZL1) is a germ cell-specific protein expressed in both male and female gonads. The DAZL1 gene, which maps to chromosome 3 in humans, is an autosomal homologue to the Deleted in AZoospermia ( DAZ) gene(s) located on the Y chromosome. We studied the expression of DAZL1 by means of immunohistochemistry in order to determine its distribution among testicular germ cell neoplasias and among the intratubular lesions in their vicinity. Our results demonstrated that expression of DAZL1 protein was consistently observed in scattered cells in all intratubular germ cell neoplasias (IGCN) of the unclassified type, as well as in some of the intratubular seminomas. Foci of DAZL1 immunopositive cells were detected in pure seminomas, while single immunopositive cells were dispersed in the seminomatous component of mixed germ cell neoplasias. All the nonseminomatous components were negative for DAZL1 expression. These findings demonstrate an antigenic heterogeneity of seminoma cells. The localization of a specific germ cell protein, DAZL1, in the putative ontogenic progenitor, IGCN, and in their putative derivative, seminoma, provides further support for the hypothesis that IGCN is the precursor of germ cell neoplasias.

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Absence of RBM expression as a marker of intratubular (in situ) germ cell neoplasia of the testis

Cited by 23 publications

References 24 publications

Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer

Nuclear expression of the RNA-binding protein RBM3 is associated with an improved clinical outcome in breast cancer

Protein Phosphatase-2Cα as a Positive Regulator of Insulin Sensitivity through Direct Activation of Phosphatidylinositol 3-Kinase in 3T3-L1 Adipocytes

Localization of a specific germ cell marker, DAZL1, in testicular germ cell neoplasias

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