1,720,997 research outputs found
Who is the boss in the Retinoblastoma family? The point of view of Rb2/p130, the little brother
No full textThis review portrays an updated overview about the possible tumor suppressive properties of the Rb2/p130 gene, the third member of the retinoblastoma (RB) family of genes, including RB itself and p107. After a brief analysis of the established structural and functional similarities among the three genes, the main purpose is to critically analyze present evidence whether Rb2/p130 shares the role of a tumor suppressor. Taking into account the well-proven growth suppressive properties of Rb2/p130 and p107, we discuss the analysis of mutated or deleted forms of Rb2/p130 found in a number of human cancers. Finally, we take into consideration the data provided by the targeted disruption of each RB family gene, alone or in combination, in the mouse model
Genetic and epigenetic alterations as hallmarks of the intricate road to cancer
No full textDespite the clonal origin of most tumors, their tremendous heterogeneity suggests that cancer progression springs from the combined forces of both genetic and epigenetic events, which produce variant clonal populations, together with the selective pressures of the microenvironment, which promote growth and, perhaps, dissemination of variants with a specific set of characteristics. Although the importance of genetic mutations in cancer has long been recognized, the role of epigenetic events has been suggested more recently. This review focuses on the genetic and epigenetic molecular mechanisms involved in cancer onset and progression, and discusses the possibility of new strategies in the development of anticancer treatments
Emerging roles of DNA tumor viruses in cell proliferation: New insights into genomic instability
No full textThe small DNA virus proteins E1A and E1B from human Adenovirus, E6 and E7 from human papillomavirus, and large T and small T antigens from SV40, are multifaceted molecular tools that can carry out an impressive number of tasks in the host cell. These viral factors, collectively termed 'oncoproteins' for their ability to induce cancer, can be viewed as paradigmatic oncogenic factors which can disrupt checkpoint controls at multiple levels - they interfere with both 'gatekeeper' cellular functions, including major control pathways of cell cycle and apoptosis, and with 'caretaker' functions, thereby inducing mitotic abnormalities and increasing genomic instability. Both E1A and E7 have been recently found to interact physically with the Ran GTPase. This interaction is key in uncoupling the centrosome cycle from the cell cycle, highlighting a direct link between viral infection and the induction of genomic instability. Further expanding our current knowledge in this field will be crucial to elucidate viral strategies leading to cellular transformation and cancer progression, as well as design novel preventive or therapeutic approaches to human cancer
Interplay between the antimetastatic nm23 and the Retinoblastoma-related Rb2/p130 genes in promoting neuronal differentiation of PC12 cells
No full textIncreasing evidence indicates that the nm23 genes, initially documented as suppressors of metastasis progression, are involved in normal development and differentiation. We have shown previously that the murine nm23 gene enhances pheochromocytoma PC12 cells responsiveness to NGF by accelerating cell growth arrest and neurite outgrowth. The present study was aimed at elucidating the mechanisms by which nm23 controls cell proliferation and promotes neuronal differentiation. We demonstrated that nm23 modulates the expression of the Rb2/p130 gene, a negative regulator of cell cycle progression also implicated in the maintenance of the differentiated state. Furthermore, we showed that nm23-H1 mutants, defective in inhibiting the invasive phenotype, downregulate Rb2/p130 expression and inhibit NGF-induced PC12 cell differentiation. In synthesis, our results provide first evidence of interplay between the nm23 and the Rb2/p130 genes in driving PC12 cells neuronal differentiation and suggest that the antimetastatic and the differentiative nm23 functions can have similar features
Retinoblastoma protein family in cell cycle and cancer: a review
No full textTwo genes, p707 and Rb2/p130, are strictly related to RE, the most investigated tumor suppressor gene, responsible for susceptibility to retinoblastoma. The products of these three genes, namely pRb, p107, and pRb2/p130 are characterized by a peculiar steric conformation, called ''pocket,'' responsible for most of the functional interactions characterizing the activity of these proteins in the homeostasis of the cell cycle. The interest in these genes and proteins springs from their ability to regulate cell cycle processes negatively, being able, for example, to dramatically slow down neoplastic growth. So far, among these genes, only RE is firmly established to act as a tumor suppressor, because its lack-of-function is clearly involved in tumor onset and progression. It has been found deleted or mutated in most retinoblastomas and sarcomas, but its inactivation is likely to play a crucial role in other types of human cancers. The two other members of the family have been discovered more recently and are currently under extensive investigation. We review analogies and differences among the pocket protein family members, in an attempt to understand their functions in normal and cancer cells. (C) 1996 Wiley-Liss, Inc
Enhancement of doxorubicin content by the antitumor drug lonidamine in resistant Ehrlich ascites tumor cells through modulation of energy metabolism
No full textThe effect of the antitumor drug lonidamine (LND) on respiration, aerobic glycolysis, adenylate pool, doxorubicin (DOX) uptake, and efflux in DOX-resistant and DOX-sensitive Ehrlich tumor cells was investigated. The results may be summarized as follows: 1) In both types of cells, LND inhibited both respiration and glycolysis in a dose-dependent manner and lowered the ATP concentration. The effect was more marked in cells incubated in glucose-free medium; 2) LND raised, to a remarkable extent, the intracellular content of DOX in resistant and sensitive cells respiring on endogenous substrates because of reduced ATP availability, whereas in glucose-supplemented medium, where both respiration and glycolysis contributed to ATP synthesis, the increase was lower; and 3) when LND was added to DOX-loaded cells, it failed to significantly inhibit DOX efflux because of time-dependent phenomena. These findings indicated that LND, a drug currently employed in tumor therapy, might also be useful in reducing or overcoming multidrug resistance (MDR) of those cells with a reduced ability to accumulate and retain antitumor drugs
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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