Interpectoral nodes metastases in breast cancer

Zhou, Xin; Jia-xiang, Yang; Liu, Xiaoyu; Ning-sheng, Zhu; Ge-li, Jiang

doi:10.1007/s11670-008-0202-1

Cited by 7 publications

(6 citation statements)

References 7 publications

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“…The myosin VI probe was prepared with a cDNA fragment from the myosin VI gene isolated from H1299 cells. The p21 and GAPDH (glyceraldehyde-3-phosphate dehydrogenase) probes were prepared as previously described (22).…”

Section: Methodsmentioning

confidence: 99%

Myosin VI Is Differentially Regulated by DNA Damage in p53- and Cell Type-dependent Manners

Cho

Chen

2010

Journal of Biological Chemistry

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Myosin VI is an unconventional motor protein and functions in a variety of intracellular processes such as cell migration, vesicular trafficking, and homeostasis of the Golgi complex. Previously, we found that myosin VI is up-regulated in RKO, LS174T, and H1299 cells by DNA damage in a p53-dependent manner and mediates the pro-survival function of p53. Here, we showed that the levels of myosin VI protein were markedly inhibited in MCF7 and LNCaP cells by topoisomerase I-II inhibitors. However, the levels of myosin VI transcript were decreased only by topoisomerase I inhibitors. We also found that the levels of myosin VI protein were markedly inhibited in MCF7 cells by wild-type p53 but not tumor-derived mutant p53. Surprisingly, we found that the level of myosin VI transcript was slightly increased instead of decreased in MCF7 cells by p53, suggesting that a mechanism other than transcriptional repression is involved. Additionally, we found that on the myosin VI promoter, the level of acetylated histone H3 was markedly decreased, whereas that of p53 and acetylated histone H4 was slightly increased in MCF7 cells upon treatment with topoisomerase I-II inhibitors. Finally, we showed that overexpression of myosin VI enhances, whereas knockdown of myosin VI decreases, DNA damage-induced stabilization of p53, and consequently, knockdown of myosin VI de-sensitizes MCF7 cells to DNA damage-induced apoptosis. Taken together, as a mediator of the p53 pro-survival pathway and a marker of malignancy in some tumors, differential regulation of myosin VI in various tumor cells by topoisomerase inhibitors dictates whether knockdown of myosin VI inhibits, rather than enhances, the susceptibility of tumor cells to some therapeutic agents, which might be explored for designing a proper therapeutic strategy.Myosins are motor proteins to move cargos along actin filaments using the energy derived from ATP hydrolysis by actinactivated Mg 2ϩ -dependent ATPase activity (1-3). Myosins are categorized into 18 distinct classes according to variations of their amino acid sequence in the motor domain. The differences in motor and tail domains are linked to their specific biological functions in the cell (4 -5). Myosin VI is an unconventional actin-based motor protein and carries out a diverse set of functions such as maintenance of the Golgi complex, cargo sorting and vesicle formation, protein secretion, endocytosis, cell migration, spindle orientation, spermatogenesis, and cell-cell contacts (1, 6 -10). In addition, myosin VI was shown to enhance RNA polymerase II-dependent transcription through physical interaction with RNA polymerase II (11), suggesting that myosin VI has a critical function in the nucleus as well as in the cytoplasm and on the plasma membrane.Myosin VI was found to be overexpressed in high-grade ovarian carcinoma cells and knockdown of myosin VI led to impediment of cell spreading, migration, and dissemination (12). Myosin VI was also found to be one of the highly expressed genes in clinical prostate specimens and knock...

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Section: Methodsmentioning

confidence: 99%

Myosin VI Is Differentially Regulated by DNA Damage in p53- and Cell Type-dependent Manners

Cho

Chen

2010

Journal of Biological Chemistry

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“…SDS-PAGE and Western blots were carried out as previously described (27). Nitrocellulose membranes were blocked with 5% dry milk in PBS with 0.1% Tween 20 (PBST) for 30 min, incubated in primary antibody overnight at 4°C or for 2 h at room temperature, and washed three times for 10 min in PBST, and then the membrane was incubated in horseradish peroxidase-conjugated secondary antibody for 1 h at room temperature and washed four times in PBST.…”

Section: Methodsmentioning

confidence: 99%

“…Northern blots were prepared using 10 g of total RNA. The P21, DKK1 (DICKKOPF-1), PIG3 (p53-induced gene-3), GADD45, FDXR, and GAPDH probes were prepared as previously described (27,28). Blots were exposed to x-ray film and quantified by densitometry.…”

Section: Methodsmentioning

confidence: 99%

The Unique NH2-terminally Deleted (ΔN) Residues, the PXXP Motif, and the PPXY Motif Are Required for the Transcriptional Activity of the ΔN Variant of p63

Helton

Zhu

Chen

2006

Journal of Biological Chemistry

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p63, a member of the p53 family of transcription factors, is known to be involved in epithelial development. However, its role in tumorigenesis is unclear. Contributing to this uncertainty, the TP63 locus can express multiple gene products from two different promoters. Utilization of the upstream promoter results in expression of the TAp63 variant with an activation domain similar to p53. In contrast, the NH 2 -terminally deleted (⌬N) p63 variant, transcribed from a cryptic promoter in intron 3, lacks such an activation domain. Thus, the TAp63 and ⌬Np63 variants possess a wide ranging ability to up-regulate p53 target genes. Consequentially, the disparity in transactivation potential between p63 variants has given rise to the hypothesis that the ⌬Np63 variant can serve as oncoprotein by opposing the activity of the TAp63 variant and p53. However, recent studies have revealed a transcriptional activity for ⌬Np63. This study was undertaken to address the transcriptional activity of the ⌬Np63 variant. Here, we showed that all NH 2 -terminally deleted p63 isoforms retain a potential in transactivation and growth suppression. Interestingly, ⌬Np63␤ possesses a remarkable ability to suppress cell proliferation and transactivate target genes, which is consistently higher than that seen with ⌬Np63␣. In contrast, ⌬Np63␥ has a weak or undetectable activity dependent upon the cell lines used. We also demonstrate that an intact DNA-binding domain is required for ⌬Np63 function. In addition, we found that the novel activation domain for the ⌬Np63 variant is composed of the 14 unique ⌬N residues along with the adjacent region, including a PXXP motif. Finally, we demonstrated that a PPXY motif shared by ⌬Np63␣ and ⌬Np63␤ is required for optimal transactivation of target gene promoters, suggesting that the PPXY motif is requisite for ⌬Np63 function.p53 functions as a tumor suppressor by transactivating target genes that mediate cell cycle arrest, apoptosis, and other p53-dependent activities. In response to DNA damage, oncogene activation, or other forms of cellular stress, p53 is stabilized by a complex series of post-translational modifications and protein-protein interactions that allow p53 to carry out its tumor suppression activity. Structurally, p53 is organized into several domains, each of which contributes to p53 transcriptional activity. p53 contains two amino-terminal activation domains, AD1 within residues 1-42 and AD2 within residues 43-92, including the proline-rich domain, which enable p53 to form direct associations with transcriptional coactivators. The DNA-binding domain allows for sequence-specific recognition of response elements in p53 target gene promoters. The tetramerization domain directs formation of the p53 tetramer required for DNA binding. Finally, the carboxyl-terminal basic domain has a regulatory function by controlling p53 stability and transcriptional activity (reviewed in Ref. 1).p63, a member of the p53 family of transcription factors, was identified in 1998 (2, 3). Like p53, p63 contains a pr...

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“…Moreover, the presence of c-Abl (ABL1) assures the enhancement of p73-induced apoptosis after treatment with 2, therefore, the subsequent redistribution of p73 might well stimulate the onset of apoptosis [80]. p73 has been reported to be involved in the cellular response to DNA damage and could activate the transcription of p53-responsive genes such as p21WAF1, Bax, Mdm2 and GADD45, and hinder cell growth in a p53-like manner by inducing apoptosis when over-expressed in cells [81]. However, in contrast to the p53 gene, mutations of p73 are rarely found in most human cancers [82,83].…”

Section: Intracellular Signalling Cascades and Cell Cycle Analysismentioning

confidence: 99%

Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC6H4Me-4] for R = Me, Et and iPr, induce apoptosis, cell cycle arrest and inhibit cell invasion of HT-29 colon cancer cells through modulation of the nuclear factor-κB activation pathway and ubiquitination

et al. 2015

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The phosphanegold(I) carbonimidothioates, Ph3PAu{SC(OR)=NC6H4Me-4} for R = Me (1), Et (2) and iPr (3), feature linear P-Au-S coordination geometries and exhibit potent in vitro cytotoxicity against HT-29 colon cancer cells in both monolayer and multi-cellular spheroid models (e.g., IC50 = 11.9 ± 0.4 and 20.3 ± 0.3 μM for 2, respectively). Both intrinsic and extrinsic pathways of apoptosis are demonstrated by human apoptosis PCR array analysis, caspase activities, DNA fragmentation and cell apoptotic assays. Compounds 1-3 induce an extrinsic pathway that leads to down-regulation of NFκB. Compound 2 also exhibits an extrinsic apoptotic pathway involving the activation of both p53 and p73, whereas 3 activates p53 only. Lys48- and Lys63-linked polyubiquitination are also promoted by 1-3. Each of cytotoxic Ph3PAu{SC(OR)=NC6H4Me-4}, for R = Me (1), Et (2) and iPr (3), induce an intrinsic apoptotic pathway as well as an extrinsic pathway leading to down-regulation of NFκB. Lys48- and Lys63-linked polyubiquitination are promoted by 1-3 and these are able to inhibit cell invasion and to suppress the activity of TrxR.

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Interpectoral nodes metastases in breast cancer

Cited by 7 publications

References 7 publications

Myosin VI Is Differentially Regulated by DNA Damage in p53- and Cell Type-dependent Manners

Myosin VI Is Differentially Regulated by DNA Damage in p53- and Cell Type-dependent Manners

The Unique NH2-terminally Deleted (ΔN) Residues, the PXXP Motif, and the PPXY Motif Are Required for the Transcriptional Activity of the ΔN Variant of p63

Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NC6H4Me-4] for R = Me, Et and iPr, induce apoptosis, cell cycle arrest and inhibit cell invasion of HT-29 colon cancer cells through modulation of the nuclear factor-κB activation pathway and ubiquitination

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