Abstract：
BACKGROUND:Incorrect 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 of retinoblastoma gene function in primary conditional Rb deficient mouse embryonic fibroblasts (MEFs). Moreover, since pRb is a transcriptional repressor, microarray analysis was done on pRb-competent and pRb-deficient MEFs to evaluate changes in expression of genes for centrosome homeostasis and for correct mitosis. RESULTS:Acute loss of pRb induces centrosome amplification and aneuploidy in the vast majority of cells analyzed. A time course analysis shows a decrease of cells with amplified centrosomes after 40 days from the adenoviral infection. At this time only 12% of cells still show amplified centrosomes. Interestingly, cells with pRb constitutive loss show a similar percentage of cells with amplified centrosomes. DNA-Chip analyses in MEFs wt (mock infected) and pRb depleted (Ad-Cre infected) cells reveal differential expression of genes controlling both centrosome duplication and mitotic progression. CONCLUSION:Our findings suggest a direct link between pRb status, centrosome amplification and chromosomal instability, and define specific mitotic genes as targets whose gene expression has to be altered to achieve or maintain aneuploidy.
journal_name
Mol Cancerjournal_title
Molecular cancerauthors
Iovino F,Lentini L,Amato A,Di Leonardo Adoi
10.1186/1476-4598-5-38subject
Has Abstractpub_date
2006-09-20 00:00:00pages
38issn
1476-4598pii
1476-4598-5-38journal_volume
5pub_type
杂志文章相关文献
Molecular Cancer文献大全abstract：BACKGROUND:An increased incidence of venous thromboembolism (VTE) is associated with anti-vascular endothelial growth factor (VEGF) treatment in cancer. However, the mechanism underlying this effect remains elusive. In this study, we examined the effect of bevacizumab, a humanized monoclonal antibody against VEGF-A, on...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/s12943-015-0418-x
更新日期：2015-07-29 00:00:00
abstract：BACKGROUND:Triple-negative breast cancer (TNBC) is highly invasive and aggressive and lacks specific molecular targets to improve the prognosis. MiR-25-3p promotes proliferation of many tumors and its role and underlying mechanisms in TNBC remain to be well elucidated. METHODS:Differential expression of miR-25-3p in T...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/s12943-017-0754-0
更新日期：2018-01-08 00:00:00
abstract：BACKGROUND:In recent years, circular RNAs (circRNAs), a new star of non-coding RNA, have been emerged as vital regulators and gained much attention for involvement of initiation and progression of diverse kinds of human diseases, especially cancer. However, regulatory role, clinical significance and underlying mechanis...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/s12943-018-0933-7
更新日期：2019-01-08 00:00:00
abstract：:Exosomes are extracellular vesicles released by many cell types and have been attributed for their roles in many diseases including cancer. Exosomes secreted by tumor cells and stromal cells are critical mediators of intercellular communication in tumor microenvironments. Long noncoding RNAs (lncRNAs) are selectively ...
journal_title：Molecular cancer
pub_type： 杂志文章,评审
doi：10.1186/s12943-018-0831-z
更新日期：2018-04-20 00:00:00
abstract：BACKGROUND:High expression of P-glycoprotein is one of the well-known mechanisms of chemoresistance in chondrosarcomas. However, the role of antiapoptotic proteins, a common mechanism responsible for chemoresistance in other tumors, has not been well studied in chondrosarcomas. We examined the importance of P-glycoprot...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-8-28
更新日期：2009-05-15 00:00:00
abstract：BACKGROUND:The survival rate of head and neck squamous cell carcinoma (HNSCC) at advanced stage is poor, despite contemporary advances in treatment modalities. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1), a single transmembrane protein without any known functional domains, is overexpressed in v...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-12-109
更新日期：2013-09-24 00:00:00
abstract：BACKGROUND:The disruption of normal gene regulation due to microRNA dysfunction is a common event in cancer pathogenesis. MicroRNA-27b is an example of an oncogenic miRNA, and it is frequently upregulated in breast cancer. MicroRNAs have been found to deregulate tumor metabolism, which typically manifests as heightened...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/s12943-018-0851-8
更新日期：2018-07-16 00:00:00
abstract：BACKGROUND:The human cell cycle transcription factor FOXM1 is known to play a key role in regulating timely mitotic progression and accurate chromosomal segregation during cell division. Deregulation of FOXM1 has been linked to a majority of human cancers. We previously showed that FOXM1 was upregulated in basal cell c...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-9-45
更新日期：2010-02-26 00:00:00
abstract：BACKGROUND:SOX2, a high mobility group (HMG)-box containing transcription factor, is a key regulator during development of the nervous system and a persistent marker of neural stem cells. Recent studies suggested a role of SOX2 in tumor progression. In our previous work we detected SOX2 in glioma cells and glioblastoma...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-10-137
更新日期：2011-11-09 00:00:00
abstract：BACKGROUND:We have previously reported that expression of the Wnt antagonist genes SFRP1 and SFRP5 is frequently silenced by promoter hypermethylation in breast cancer. SFRP2 is a further Wnt inhibitor whose expression was recently found being downregulated in various malignancies. Here we investigated whether SFRP2 is...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-7-83
更新日期：2008-11-06 00:00:00
abstract：BACKGROUND:N6-methyladenosine (m6A) emerges as one of the most important modification of RNA. Bladder cancer is a common cancer type in developed countries, and hundreds of thousands of bladder cancer patients die every year. MATERIALS AND METHODS:There are various cells in bladder tumor bulk, and a small population c...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/s12943-019-1084-1
更新日期：2019-11-25 00:00:00
abstract：:Bortezomib is a novel anti-cancer agent which has shown promising activity in non-small lung cancer (NSCLC) patients. However, only a subset of patients respond to this treatment. We show that NSCLC cell lines are differentially sensitive to bortezomib, IC50 values ranging from 5 to 83 nM. The apoptosis-inducing poten...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-6-73
更新日期：2007-11-17 00:00:00
abstract：BACKGROUND:Patients with familial adenomatous polyposis (FAP) are at increased risk for the development of colorectal cancer. Surgery and chemoprevention are the most effective means to prevent cancer development. Thymoquinone (TQ) is considered the main compound of the volatile Nigella sativa seed oil and has been rep...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-12-41
更新日期：2013-05-13 00:00:00
abstract：BACKGROUND:The human genome encodes thousands of unique long non-coding RNAs (lncRNAs), and these transcripts are emerging as critical regulators of gene expression and cell fate. However, the transcriptional regulation of their expression is not fully understood. The pivotal transcription factor E2F1 which can induce ...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-12-131
更新日期：2013-10-29 00:00:00
abstract：BACKGROUND:Long non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application o...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/s12943-020-01232-3
更新日期：2020-07-15 00:00:00
abstract：BACKGROUND:Osteopontin (OPN) has been shown to play many roles in the progression of cancer. We have recently demonstrated the activation of Akt by OPN. Integrin-linked kinase and PI3-kinase are integral proteins in OPN/AKT pathway in PC3 cells. To investigate the role of the extracellular receptors in OPN signaling, w...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-9-260
更新日期：2010-09-26 00:00:00
abstract：BACKGROUND:Oncolytic virotherapy is an attractive drug platform of cancer gene therapy, but efficacy and specificity are important prerequisites for success of such strategies. Previous studies determined that Apoptin is a p53 independent, bcl-2 insensitive apoptotic protein with the ability to specifically induce apop...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-9-10
更新日期：2010-01-20 00:00:00
abstract：BACKGROUND:Cancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recen...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/s12943-017-0653-4
更新日期：2017-04-26 00:00:00
abstract：BACKGROUND:Certain types of potassium channels (known as Eag1, KCNH1, Kv10.1) are associated with the production of tumours in patients and in animals. We have now studied the expression pattern of the Eag1 channel in a large range of normal and tumour tissues from different collections utilising molecular biological a...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-5-41
更新日期：2006-10-05 00:00:00
abstract：BACKGROUND:An increasing number of studies support the presence of stem-like cells in human malignancies. These cells are primarily responsible for tumor initiation and thus considered as a potential target to eradicate tumors. CD133 has been identified as an important cell surface marker to enrich the stem-like popula...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-9-39
更新日期：2010-02-19 00:00:00
abstract：BACKGROUND:Aspartate β-hydroxylase (ASPH) is silent in normal adult tissues only to re-emerge during oncogenesis where its function is required for generation and maintenance of malignant phenotypes. Exosomes enable prooncogenic secretome delivering and trafficking for long-distance cell-to-cell communication. This stu...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/s12943-019-1077-0
更新日期：2019-11-07 00:00:00
abstract：BACKGROUND:Cellular senescence is a state of irreversible cell growth arrest and senescence cells permanently lose proliferation potential. Induction of cellular senescence might be a novel therapy for cancer cells. TRIB2 has been reported to participate in regulating proliferation and drug resistance of various cancer...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/s12943-018-0922-x
更新日期：2018-12-12 00:00:00
abstract：BACKGROUND:MUC16 is a cell surface mucin expressed at high levels by epithelial ovarian tumors. Following proteolytic cleavage, cell surface MUC16 (csMUC16) is shed in the extracellular milieu and is detected in the serum of cancer patients as the tumor marker CA125. csMUC16 acts as an adhesion molecule and facilitates...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-9-118
更新日期：2010-05-24 00:00:00
abstract：:Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases worldwide. It is refractory to conventional treatments, and consequently has a documented 5-year survival rate as low as 7%. Increasing evidence indicates that activated pancreatic stellate cells (PSCs), one of the stromal components ...
journal_title：Molecular cancer
pub_type： 杂志文章,评审
doi：10.1186/s12943-018-0815-z
更新日期：2018-02-19 00:00:00
abstract：:The correlation between epigenetic aberrations and disease underscores the importance of epigenetic mechanisms. Here, we review recent findings regarding chromatin modifications and their relevance to cancer. ...
journal_title：Molecular cancer
pub_type： 杂志文章,评审
doi：10.1186/1476-4598-5-60
更新日期：2006-11-08 00:00:00
abstract：BACKGROUND:Antisense (AS) induced down-regulation of uPAR in ACCS adenoid-cyctic carcinoma cells decreased the cellular adhesion and invasion on various extracellular matrices. Additionally, ACCS-AS cells showed an increased EGFR expression and other behavioral similarities to NA-SCC, a typical highly proliferative but...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-7-47
更新日期：2008-06-03 00:00:00
abstract：:Tumor metabolism is a thrilling discipline that focuses on mechanisms used by cancer cells to earn crucial building blocks and energy to preserve growth and overcome resistance to various treatment modalities. At the same time, therapies directed specifically against aberrant signalling pathways driven by protein tyro...
journal_title：Molecular cancer
pub_type： 杂志文章,评审
doi：10.1186/s12943-018-0798-9
更新日期：2018-02-19 00:00:00
abstract：BACKGROUND:Tumor spreading is the major threat for cancer patients. The recently published anti-cancer drug salinomycin raised hope for an improved treatment by targeting therapy-refractory cancer stem cells. However, an unambiguous role of salinomycin against cancer cell migration and metastasis formation remains elus...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-13-16
更新日期：2014-01-27 00:00:00
abstract：:Hepatocellular carcinoma (HCC) is one of the most common malignant tumours with a poor prognosis worldwide. While early stage tumours can be treated with curative approaches such as liver transplantation or surgical resection, these are only suitable for a minority of patients. Those with advanced stage disease are on...
journal_title：Molecular cancer
pub_type： 杂志文章,评审
doi：10.1186/s12943-017-0734-4
更新日期：2017-10-23 00:00:00
abstract：BACKGROUND:SLC/CCL21, normally expressed in high endothelial venules and in T cell zones of spleen and lymph nodes, strongly attracts T cells and dendritic cells (DC). We have previously shown that SLC/CCL21-mediated anti-tumor responses are accompanied by significant induction of IFNgamma and the CXC chemokines, monok...
journal_title：Molecular cancer
pub_type： 杂志文章
doi：10.1186/1476-4598-2-22
更新日期：2003-04-15 00:00:00
