Overexpressed TP73 induces apoptosis in medulloblastoma

Castellino, Robert C.; Bortoli, Massimiliano De; Lin, Linda L.; Skapura, Darlene G.; Rajan, Jessen A; Adesina, Adekunle M.; Perlaky, László; Irwin, Meredith S.; Kim, John Y.H.

doi:10.1186/1471-2407-7-127

Cited by 40 publications

(40 citation statements)

References 44 publications

(52 reference statements)

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“…The percentage sub-G 0 /G 1 peak in the hypodiploid distribution below a DNA index of one (< 2n) and the percentage of proliferating cells (S phase) were calculated. Because the nucleus becomes fragmented during apoptosis and numerous individual chromatin fragments may be present in a single cell, the percentage of objects with a fractional DNA content is represented by the sub-G 0 /G 1 peak (Castellino et al 2007). For each analysis, 10,000 cells were acquired.…”

Section: Methodsmentioning

confidence: 99%

Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

Silva¹,

Silva²,

Baruque³

et al. 2008

Mem. Inst. Oswaldo Cruz

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Section: Methodsmentioning

confidence: 99%

Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

Silva¹,

Silva²,

Baruque³

et al. 2008

Mem. Inst. Oswaldo Cruz

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“…However, the level of mRNA might be different from the actual level of the protein due to the different stability of transcripts and/or different posttranslational modifications and protein turnover dynamics. This discordance was confirmed in medulloblastomas as transcript amounts of TAp73 and DNp73 were almost similar in Daoy cells, but there was a higher amount of TAp73 protein detected compared to that of DNp73 (Castellino et al 2007). For this reason, we studied p73 at the protein level.…”

Section: Discussionmentioning

confidence: 55%

Analysis of the intracellular localization of p73 N-terminal protein isoforms TAp73 and ∆Np73 in medulloblastoma cell lines

et al. 2010

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The protein homologous to the tumor suppressor p53, p73, has essential roles in development and tumorigenesis. This protein exists in a wide range of isoforms with different, even antagonistic, functions. However, there are virtually no detailed morphological studies analyzing the endogenous expression of p73 isoforms at the cellular level in cancer cells. In this study, we investigated the expression and subcellular distribution of two N-terminal isoforms, TAp73 and ΔNp73, in medulloblastoma cells using immunofluorescence microscopy. Both proteins were observed in all cell lines examined, but differences were noted in their intracellular localization between the reference Daoy cell line and four newly established medulloblastoma cell lines (MBL-03, MBL-06, MBL-07 and MBL-10). In the new cell lines, TAp73 and ΔNp73 were located predominantly in cell nuclei. However, there was heterogeneity in TAp73 distribution in the cells of all MBL cell lines, with the protein located in the nucleus and also in a limited non-random area in the cytoplasm. In a small percentage of cells, we detected cytoplasmic localization of TAp73 only, i.e., nuclear exclusion was observed. Our results provide a basis for future studies on the causes and function of distinct intracellular localization of p73 protein isoforms with respect to different protein-protein interactions in medulloblastoma cells.

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“…While, on the other hand, the N-terminally p73 isoforms such as delta Np73, ex2p73, and ex2/3p73, which have been found to be highly expressed in many cancers, possess anti-apoptotic activities [54]. Interesting though, there is also evidence that the deltaNp73 isoform can exhibit apoptotic activity when overexpressed [55] as also other deltaNp73 isoforms while targeting p53 specific genes [55]. Given the specificity of the antibody used for p73 in our study we cannot be sure about which p73 isoform is being detected though the antibody was cited to be able to detect all p73 isoforms if present meaning even in the 70 Kda and 55 Kda range corresponding to the TAp73 isoforms (α,β,γ,δ,ε,η,ζ) [54,56] though we were not able to detect any bands at that height.…”

Section: Discussionmentioning

confidence: 99%

NSP 5a3a: A Potential Novel Cancer Target in Head and Neck Carcinoma

D’Agostino

Giordano

2010

Oncotarget

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AbstrAct:NSP 5a3a along with three other distinct though similar splice variants were initially identified corresponding to locus HCMOGT-1 on chromosome 17p11. Subsequent investigation, elucidated NSP 5a3a's potential involvement in cellular processes such as ribosome biogenesis and rRNA processing by validating NSP 5a3a's novel interaction with B23 and ribonuclear protein hnRNP-L possibly implicating NSP 5a3a's involvement in cellular activities such as RNA metabolism and processing [4]. In this preliminary investigation, we wanted to observe the effect that over-expressing NSP 5a3a may have on cell cycle and its potential application in cancer treatment in aggressive cancers such as head and neck carcinomas. Over-expressed NSP 5a3a in HN30 cells induced a significant degree of apoptosis, an average of a 10.85 fold increase compared to controls 3 days post-transfection. This effect was more significant then the apoptosis observed between Fadu cells over-expressing NSP 5a3a and its controls. Though, the apoptosis induced in the WI38 control cell line showed an average of a 13.2 fold increase between treated and controls comparable to the HN30 cell line 3 days post-transfection. Molecular analysis indentified a novel p73 dependent mechanism independent of p53 and caspase 3 activity through which NSP 5a3a is inducing apoptosis. We propose NSP 5a3a as a potential therapeutic target for site directed cancer treatment in perhaps certain head and neck carcinomas by induction of apoptosis.

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Overexpressed TP73 induces apoptosis in medulloblastoma

Cited by 40 publications

References 44 publications

Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

Morphological and functional characterizations of Schwann cells stimulated with Mycobacterium leprae

Analysis of the intracellular localization of p73 N-terminal protein isoforms TAp73 and ∆Np73 in medulloblastoma cell lines

NSP 5a3a: A Potential Novel Cancer Target in Head and Neck Carcinoma

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