showing 20 related works from this author
Centrosome amplification induced by hydroxyurea leads to aneuploidy in pRB deficient human and mouse fibroblasts.
2006
Alterations in the number and/or morphology of centrosomes are frequently observed in human tumours. However, it is still debated if a direct link between supernumerary centrosomes and tumorigenesis exists and if centrosome amplification could directly cause aneuploidy. Here, we report that hydroxyurea treatment induced centrosome amplification in both human fibroblasts expressing the HPV16 -E6-E7 oncoproteins, which act principally by targeting p53 and pRB, respectively, and in conditional pRB deficient mouse fibroblasts. Following hydroxyurea removal both normal and p53 deficient human fibroblasts arrested. On the contrary pRB deficient fibroblasts entered the cell cycle generating aneupl…
Chromosomal instability promoted by RB depletion relied neither on p53 nor SAC dysfunction in HCT116 tumor cells
2008
The mitotic kinase Aurora-A promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERα+ breast cancer cells
2013
In this study, we demonstrate that constitutive activation of Raf-1 oncogenic signaling induces stabilization and accumulation of Aurora-A mitotic kinase that ultimately drives the transition from an epithelial to a highly invasive mesenchymal phenotype in estrogen receptor α-positive (ERα(+)) breast cancer cells. The transition from an epithelial- to a mesenchymal-like phenotype was characterized by reduced expression of ERα, HER-2/Neu overexpression and loss of CD24 surface receptor (CD24(-/low)). Importantly, expression of key epithelial-to-mesenchymal transition (EMT) markers and upregulation of the stemness gene SOX2 was linked to acquisition of stem cell-like properties such as the ab…
RNAi mediated acute depletion of Retinoblastoma protein (pRb) promotes aneuploidy in human primary cells via micronuclei formation
2009
BACKGROUND: Changes in chromosome number or structure as well as supernumerary centrosomes and multipolar mitoses are commonly observed in human tumors. Thus, centrosome amplification and mitotic checkpoint dysfunctions are believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor (RB) participates in the regulation of synchrony between DNA synthesis and centrosome duplication and it is involved in transcription regulation of some mitotic genes. Primary human fibroblasts were transfected transiently with short interfering RNA (siRNA) specific for human pRb to investigate the effects of pRb acute loss on chromosomal stability. RESULTS: Acutely pRb-depleted fibr…
Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype
2007
Abstract Background Genetic instability is a hallmark of tumours and preneoplastic lesions. The predominant form of genome instability in human cancer is chromosome instability (CIN). CIN is characterized by chromosomal aberrations, gains or losses of whole chromosomes (aneuploidy), and it is often associated with centrosome amplification. Centrosomes control cell division by forming a bipolar mitotic spindle and play an essential role in the maintenance of chromosomal stability. However, whether centrosome amplification could directly cause aneuploidy is not fully established. Also, alterations in genes required for mitotic progression could be involved in CIN. A major candidate is represe…
Transient and stable depletion of RB induce different expression of genes involved in epigenetic modifications.
2008
Transient silencing of MAD2 induces mitotic abnormalities and p21waf1 overexpression in primary human fibroblasts
2007
NOTCH3 expression is linked to breast cancer seeding and distant metastasis
2018
Background Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive. Methods We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF…
Micronuclei generation and chromosomal instability after RB interferences in human fibroblasts
2007
RB acute loss induces centrosome amplification and aneuploidy in murine primary fibroblasts
2006
AbstractBackgroundIncorrect segregation of whole chromosomes or parts of chromosome leads to aneuploidy commonly observed in cancer. The correct centrosome duplication, assuring assembly of a bipolar mitotic spindle, is essential for chromosome segregation fidelity and preventing aneuploidy. Alteration of p53 and pRb functions by expression of HPV16-E6 and E7 oncoproteins has been associated with centrosome amplification. However, these last findings could be the result of targeting cellular proteins in addition to pRb by HPV16-E7 oncoprotein. To get a more detailed picture on the role of pRb in chromosomal instability and centrosome amplification, we analyzed the effects of the acute loss …
Low doses of Hydroxyurea induce centrosome amplification and aneuploidy in primary human fibroblasts in culture
2007
Aurora-A Transcriptional Silencing and Vincristine Treatment Show a Synergistic Effect in Human Tumor Cells
2008
Aurora-A is a centrosome-associated serine/threonine kinase that is overexpressed in multiple types of human tumors. Primarily, Aurora-A functions in centrosome maturation and mitotic spindle assembly. Overexpression of Aurora-A induces centrosome amplification and G 2 /M cell cycle progression. Recently, it was observed that overexpression of Aurora-A renders cells resistant to cisplatin (CDDP)-, etoposide-, and paclitaxel-induced apoptosis.Our results indicate that already in initial stages of cancer progression Aurora-A overexpression could have a major role in inducing supernumerary centrosomes and aneuploidy, as shown by immunohistochemistry on tissue sections from various stages of hu…
CENPA overexpression promotes genome instability in pRb-depleted human cells
2009
Abstract Background Aneuploidy is a hallmark of most human cancers that arises as a consequence of chromosomal instability and it is frequently associated with centrosome amplification. Functional inactivation of the Retinoblastoma protein (pRb) has been indicated as a cause promoting chromosomal instability as well centrosome amplification. However, the underlying molecular mechanism still remains to be clarified. Results Here we show that pRb depletion both in wild type and p53 knockout HCT116 cells was associated with the presence of multipolar spindles, anaphase bridges, lagging chromosomes and micronuclei harbouring whole chromosomes. In addition aneuploidy caused by pRb acute loss was…
DNMT1 transient silencing induces aneuploidy, premature separated chromatids and centromeric chromatin alterations
2008
Additional file 4: of NOTCH3 expression is linked to breast cancer seeding and distant metastasis
2018
Figure S4. CRISPR-NOTCH3 breast cancer cells. a NOTCH3 gene knockout using CRISPR/Cas9. Lightning bolt symbols indicate the targeted gene double-stranded break (DSB) sites for different sgRNAs F1 and R2. Horizontal arrows show the PCR primers designed at different chromosomal sites to identify deletions. b A PCR product of ~â 650-bp size is amplified upon a successful double-hit by SRISPR/Cas9 system. c Secondary screening using internal primers. Internal primers were used to screen for clones with efficient gene knockout. Clone 416 was selected for further verification by immunoblot assay (Fig. 4a). (TIFF 6168 kb)
Additional file 1: of NOTCH3 expression is linked to breast cancer seeding and distant metastasis
2018
Figure S1. Expression of CD24 luminal marker in MPS derived from variant vMCF-7∆Raf1 and vMCF-7∆Raf1 1GX-M cells. a Immunofluorescence analysis showing representative images of vMCF-7∆Raf1 and vMCF-7∆Raf1 1GX-M MPS stained in red with a CD24 monoclonal antibody. Nuclei were stained in blue with 4′,6-diamidino-2-phenylindole (DAPI). b Graph showing the average number of CD24-expressing cells from three independent experiments (± SD). (TIFF 6168 kb)
Additional file 2: of NOTCH3 expression is linked to breast cancer seeding and distant metastasis
2018
Figure S2. Transcriptomic characterization of metastatic breast cancer cells. a Comparative global gene array analysis between CD24â /low (isolated by FACS sorting from vMCF-7Raf-1 1GX cells) and vMCF-7Raf-1 1GX-M MPS. b In silico comparative functional enrichment analysis between CD24â /low (isolated from vMCF-7Raf-1 1GX cells) and vMCF-7Raf-1 1GX-M MPS identified 59 genes involved in nuclear reprograming. (TIFF 6168 kb)
Additional file 5: of NOTCH3 expression is linked to breast cancer seeding and distant metastasis
2018
Figure S5. NOTCH1 and NOTCH2 expression in TNBC cells. a Immunofluorescence analysis showing representative images of MDA-MB-231 and MDA-MB-231 LM TNBC cells stained in green with NOTCH1 and NOTCH2 polyclonal antibodies. Nuclei were stained in blue with DAPI. b Graphs showing the average number of NOTCH1- and NOTCH2-expressing cells from three independent experiments (Âąâ SD). (TIFF 6168 kb)
Additional file 6: of NOTCH3 expression is linked to breast cancer seeding and distant metastasis
2018
Figure S6. NOTCH1 and NOTCH2 expression in patient-derived TNBC cells. a Immunoblot assay showing NOTCH1 and NOTCH2 expression in MDA-MB-231 and patient-derived TNBC-M25 cells. b Densitometric analysis showing the percentage of NOTCH1 and NOTCH2 protein levels in TNBC-M25 cells relative to MDA-MB-231 cells. Graph showing the average from three independent experiments (Âąâ SD). (TIFF 6168 kb)
Additional file 3: of NOTCH3 expression is linked to breast cancer seeding and distant metastasis
2018
Figure S3. Expression of genes identified in NOTCH3 metastatic network. Graphs showing the average expression values in sample replicates (from two independent experiments Âą SD) for each gene represented in the NOTCH3 metastatic network. (TIFF 6168 kb)