Loop domain organization of the p53 locus in normal and breast cancer cells correlates with the transcriptional status of the TP53 and the neighboring genes

Góes, Andréa Carla de Souza; Cappellen, David; Santos, Gilson Costa dos; Pirozhkova, Iryna; Lipinski, Marc; Vassetzky, Yegor S.; Moura-Gallo, Claudia V. De

doi:10.1002/jcb.23129

Cited by 5 publications

(8 citation statements)

References 33 publications

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“…[33] found that in natural aging of the rat liver, the average DNA loop size gradually decreases, and DNA loops increase in number with the gradual loss of proliferating potential and with the progression towards terminal differentiation. More recently, it has been shown that in breast cancer cell lines the dimension of chromatin loops are larger as compared to that of normal cells [34]. These results are in agreement with the data reported above.…”

Section: Discussionsupporting

confidence: 91%

The Role of Nuclear Matrix Proteins Binding to Matrix Attachment Regions (MARs) in Prostate Cancer Cell Differentiation

et al. 2012

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In tumor progression definite alterations in nuclear matrix (NM) protein composition as well as in chromatin structure occur. The NM interacts with chromatin via specialized DNA sequences called matrix attachment regions (MARs). In the present study, using a proteomic approach along with a two-dimensional Southwestern assay and confocal laser microscopy, we show that the differentiation of stabilized human prostate carcinoma cells is marked out by modifications both NM protein composition and bond between NM proteins and MARs. Well-differentiated androgen-responsive and slowly growing LNCaP cells are characterized by a less complex pattern and by a major number of proteins binding MAR sequences in comparison to 22Rv1 cells expressing androgen receptor but androgen-independent. Finally, in the poorly differentiated and strongly aggressive androgen-independent PC3 cells the complexity of NM pattern further increases and a minor number of proteins bind the MARs. Furthermore, in this cell line with respect to LNCaP cells, these changes are synchronous with modifications in both the nuclear distribution of the MAR sequences and in the average loop dimensions that significantly increase. Although the expression of many NM proteins changes during dedifferentiation, only a very limited group of MAR-binding proteins seem to play a key role in this process. Variations in the expression of poly (ADP-ribose) polymerase (PARP) and special AT-rich sequence-binding protein-1 (SATB1) along with an increase in the phosphorylation of lamin B represent changes that might trigger passage towards a more aggressive phenotype. These results suggest that elucidating the MAR-binding proteins that are involved in the differentiation of prostate cancer cells could be an important tool to improve our understanding of this carcinogenesis process, and they could also be novel targets for prostate cancer therapy.

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Section: Discussionsupporting

confidence: 91%

The Role of Nuclear Matrix Proteins Binding to Matrix Attachment Regions (MARs) in Prostate Cancer Cell Differentiation

et al. 2012

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“…The tumor suppressor gene TP53 is one of the most studied genes implicated in cancer and, despite a huge knowledge on its post-translational regulation [31,32], its transcription control and genomic domain are not very well established [33]. In a previous work we described MARs in a genomic region of 167 kb containing the TP53 and neighboring genes, using different cell lines [27]. Here we concentrated our study on two MARs, namely MAR2 and MAR3.…”

Section: Results and Discussion Association Of S/mars In Breast Cellmentioning

confidence: 99%

“…1, A). This organization is perturbed in cancerous cell lines MDA-MB-231, BT-474, T47D and MCF-7 [27]. Chromatin is composed of DNA and proteins, mostly histones, which are involved in genomic DNA organization in the nuclei.…”

Section: Results and Discussion Association Of S/mars In Breast Cellmentioning

confidence: 99%

“…However, as nuclear matrix remains a controversial concept [13] and the data on the interplay between MARs and histone epigenetic chromatin status are still absent, we decided to test whether the association of S/MARs with the nuclear matrix in breast cancer cell lines corresponds to specific chromatin modifications. We have previously mapped S/MARs in the 167 kb locus of the tumor suppressor gene TP53 in cancerous breast cell lines, MDA-MB-231, BT-474, T47D, MCF-7, and non-cancerous breast cell lines, MCF10A and HB2, using DNA arrays [27]. We found that the loop domain organization in these cell lines was quite variable.…”

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confidence: 98%

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Chromatin enrichment of histone marks H4Ac and H3K9me3 in TP53 gene domain in breast cells

2014

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In non-cancerous breast cell lines HB2 and MCF10A the TP53 gene is localized inside a relatively small~50 kb loop domain delimited by two S/MARs. Aim. To analyze the chromatin markers H4Ac and H3K9me3 of these two S/MARs and of the TP53 gene P1 promoter in different breast cells lines. Methods. We used chromatin immunoprecipitation (ChIP) to characterize the chromatin status of these S/MARs elements in breast non-cancerous cell lines HB2 and MCF10A and cancerous MCF-7, MDA-MB-231, BT-474 and T47D cell lines, by chromatin enrichment of H4Ac and H3K9me3 epigenetic markers, hallmarks of open and closed chromatin, respectively. Results. We found that these chromatin epigenetic markers are differentially distributed in S/MARs for all analyzed breast cell lines. Conclusions. We found no correlation between S/MARs and chromatin epigenetic status, suggesting that nuclear matrix fixation and chromatin status can be independent. High enrichment of H3K9me3 in the TP53 gene P1 promoter region in MCF-7, could explain lower levels of the TP53 expression, described earlier by our group.

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“…HB2 cells were selected for their ability to undergo branching morphogenesis from spherical structures when cultured in collagen gels and stimulated by hepatocyte growth factor and used as a cell model system for the study of the involvement of fibroblast-derived growth factor, Wnt, and integrins in mammary tissue development (Huguet et al 1995;Alford et al 1998). Subsequently, HB2 cells have been used as non-neoplastic counterpart for elucidating various biochemical and genetical aspects of normal and tumoral breast cell biology, such as Wnt5a-and heregulinstimulated signal transduction pathways (e.g., Baeckström et al 2000a;Jönsson and Andersson 2001;Dejmek et al 2003), c-ERBb2 promotion of apoptosis and effect on MUC1 expression (e.g., Baeckström et al 2000b;Scibetta et al 2001), ethanol promotion of cell invasion (e.g., Aye et al 2004), cadmium-mediated changes in gene expression (Sirchia et al 2008;Sirchia and Luparello 2009), TP53 transcriptional regulation (Goes et al 2011), and epigenetic modulation of oncosuppressor genes (Rubinek et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic characterization of HB2 epithelial cells from the human breast

Caradonna

Luparello

2013

In Vitro Cell.Dev.Biol.-Animal

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HB2 is a cell line originated by subcloning of MTSV1-7 mammary luminal epithelial cells isolated from human milk and immortalization via introduction of the gene encoding simian virus 40 (SV40) large T antigen. Despite its wide utilization as non-neoplastic counterpart in assays aimed to elucidating various biochemical and genetical aspects of normal and tumoral breast cells, to our knowledge no literature data have so far appeared concerning the chromosomal characterization of the HB2 cells. Here, we report the cytogenetic characterization of the karyotype of HB2 cells, which puts in evidence the occurrence of changes in chromosomal number and structure and the presence of unidentified chromosomal markers in variable amount. Our results do not detract from the utility of HB2 cells in illustrating fundamental aspects of breast cell biology, but rather interject a note of caution into generalizing results obtained with this cell line to other non-immortalized epithelial cell populations from the human breast. Therefore, this work represents a useful resource for all who want to perform appropriate and focused future studies on this cell line and proposes precise indications for a knowledgeable use of HB2 cells.

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Loop domain organization of the p53 locus in normal and breast cancer cells correlates with the transcriptional status of the TP53 and the neighboring genes

Cited by 5 publications

References 33 publications

The Role of Nuclear Matrix Proteins Binding to Matrix Attachment Regions (MARs) in Prostate Cancer Cell Differentiation

The Role of Nuclear Matrix Proteins Binding to Matrix Attachment Regions (MARs) in Prostate Cancer Cell Differentiation

Chromatin enrichment of histone marks H4Ac and H3K9me3 in TP53 gene domain in breast cells

Cytogenetic characterization of HB2 epithelial cells from the human breast

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