|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Here, we establish a naturally occurring model of cancer susceptibility due to CDKN2 dysregulation, thus providing insight about this cancer-associated, complex, and poorly understood genomic region.
|
22623710 |
2012 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Our results establish that CDK2 activity is necessary for normal mammalian cell cycle progression and suggest that it might be a useful therapeutic target for treating cancer.
|
22474407 |
2012 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Finally, our findings highlight that pharmacological inhibition of Cdk2 activity is a potential therapeutical principle for cancer therapy, in particular for tumors with activated Myc or Ras.
|
19966300 |
2010 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Cyclin-dependent kinase 2 (CDK2) is a member of serine/ threonine protein kinases, which initiates the principal transitions of the eukaryotic cell cycle and is a promising target for cancer therapy.
|
20423616 |
2010 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding.
|
20399812 |
2010 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Our data provide insight into the mechanism by which CDK2 is regulated and the molecular basis of cell cycle progression in cancer.
|
19829063 |
2009 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
First, CDK2 activity was increased in the absence of estrogen or in the presence of estrogen antagonists tamoxifen or ICI 182780; second, amplified in breast cancer 1 (AIB1), a cancer overexpressed transcriptional coactivator, was hyperphosphorylated, which made AIB1 a better coactivator for E2F1; and third, growth factor receptor binding protein 2-associated binder 2 (Gab2) and Akt activity were increased following E2F1 overactivation, leading to a significant enhancement of cell migration and invasion.
|
17804714 |
2007 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Thus, KAP regulates both cdc2-dependent migration and Cdk2-dependent proliferation, and its loss due to aberrant splicing increases malignancy in human gliomas.
|
17210692 |
2007 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In contrast, inactivation of pRb, the key component of the pathway, activated the DDR in cultured human or mouse cells, analogous to elevated cyclin E. These results highlight differential effect of diverse oncogenic events on driving the 'cancer cell cycles' and their ability to deregulate the replication-driving CDK2 kinase and to alarm the DDR as a potential anticancer barrier in accordance with their hierarchical positions along the retinoblastoma pathway.
|
17079443 |
2006 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Between borderline and malignant tumors, the increased expression levels of P53, Bax, Cyclin E, and cyclin-dependent kinase-2 as well as the decreased expression levels of growth arrest and DNA damage (GADD45) and murine double minute-2 (MDM2) were significantly associated with malignancy (P < 0.01, each).
|
15882169 |
2005 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Three known tumor suppressor genes, p16/CDKN2, BRCA2, and p53, all of which are important in the development of pancreatic carcinoma and frequently are involved in a variety of cancer syndromes, were analyzed.
|
15112280 |
2004 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
Taken together, we identified testicular interaction partners of the cyclin A1-CDK2 complex and studied their expression pattern in normal organs, testis development, and testicular malignancies.
|
15159402 |
2004 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Deregulation of cyclin E, an activator of cyclin-dependent kinase 2 (Cdk2), has been associated with a broad spectrum of human malignancies.
|
15048079 |
2004 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Here we report of sustained cell proliferation in the absence of CDK2, and we suggest that CDK2 is not a suitable target for cancer therapy.
|
12676582 |
2003 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Dysregulation of the CDK2-bound cyclins plays an important role in the pathogenesis of cancer.
|
14510182 |
2003 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The prevailing view of cdk2 as a critical regulator of cell cycle progression and optimal therapeutic target in cancer cells is now challenged by the observation that tumor cells deficient in cdk2 protein and kinase activity are not impaired in proliferation.
|
12726855 |
2003 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
This substitution afforded agents with increased potency relative to the parent indolinone and nanomolar range IC(50) against the CDK2 enzyme and two cancer cell lines.
|
12659774 |
2003 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
By contrast, abrogation of the p57KIP2 gene expression and increased expression of G1 cyclins (cyclin E) and G1 CDKs (CDK2 and CDK4) were associated with high activity of G1 cyclin-CDK complexes in malignant tumors and in the H295R cell line.
|
10634406 |
2000 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
In astrocytomas low CDKN2/p16 expression was associated with high histologic malignancy grade (p = 0.002): CDKN2/p16 protein level was decreased in 9 out of 10 glioblastomas, in 5 out of 9 anaplastic astrocytomas, in 3 out of 10 grade II astrocytomas and in none of pilocytic astocytomas (0/7).
|
10359140 |
1999 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
Inactivation of the tumor-suppressor gene p16 (MTS1/ CDKN2/INK4a) has been described in various human malignancies.
|
9495360 |
1998 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Inactivation of the CDKN2/p16(INK4A) tumor-suppressor gene is one of the most frequent genetic alterations in human malignancies.
|
9834265 |
1998 |
|
Malignant Neoplasms
|
0.100 |
Biomarker
|
group |
BEFREE |
The CDKN2 gene appears to be the major tumor suppressor gene on chromosome 9p21, and it is thought to be involved in the tumorigenesis of various lymphoid malignancies.
|
9086436 |
1997 |
|
Malignant Neoplasms
|
0.100 |
AlteredExpression
|
group |
BEFREE |
It is becoming clear that a common feature of cancer cells is the abrogation of cell cycle checkpoints, either by aberrant expression of positive regulators (for example, cyclins and CDKs) or the loss of negative regulators, including p21Cip1 through loss of function of its transcriptional activator p53, or deletion or mutation of p16ink4A (multiple tumor suppressor 1/CDKN2) and the retinoblastoma tumor suppressor protein.
|
9149259 |
1997 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.
|
9328469 |
1997 |
|
Malignant Neoplasms
|
0.100 |
GeneticVariation
|
group |
BEFREE |
Loss of expression of the p16INK4 tumor suppressor protein, the product of the CDKN2 gene, has been associated with a wide variety of human malignancies.
|
9221801 |
1997 |