Journal Article

Cooperative alterations of <i>Rb</i> pathway regulators in mouse primary T cell lymphomas

I. Pérez de Castro, M. Malumbres, J. Santos, A. Pellicer and J. Fernández-Piqueras

in Carcinogenesis

Volume 20, issue 9, pages 1675-1682
Published in print September 1999 | ISSN: 0143-3334
Published online September 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.9.1675
Cooperative alterations of Rb pathway regulators in mouse primary T cell lymphomas

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Alterations in the Rb pathway have been described in many different tumors. In order to study this cell cycle regulatory mechanism in murine T cell lymphomas, we have analyzed the RNA and protein expression of the cyclin D1, cdk4 and retinoblastoma genes in primary tumor samples. We have detected overexpression of the cyclin D1 gene and deficient expression of the retinoblastoma gene in 42 and 28% of these tumors, respectively. The immunohistochemical analysis showed that these RT–PCR results are correlated with a significant increase in the number of positive cells for cyclin D1 and a moderate decrease in the expression of Rb protein, respectively. The analysis of cyclin D1, Rb, p15INK4b and p16INK4a showed that 75% of lymphomas had alterations in these genes and indicates that the Rb pathway is frequently altered in mouse primary T cell lymphomas. Moreover, 31% of lymphomas presented simultaneous alterations in at least two of these genes, suggesting the importance of concurrent alteration of different Rb pathway regulators. In addition, we have characterized these samples for mutational status of the N-ras and K-ras genes. We have only detected mutations in codon 12 of K-ras in six of 49 lymphomas (12%). Interestingly, five of these lymphomas also showed alterations in at least one of the Rb pathway regulators analyzed here. Taken together, these data suggest that deregulation of the Rb pathway regulators and/or oncogenic activation of K-ras may represent a common important clue in progression of murine T cell lymphomas.

Keywords: DAB, diaminobenzidine; NMU, N-methyl-N-nitrosourea; TLSR1, thymic lymphoma suppressor region 1.

Journal Article.  6703 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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