Modulation of CDK2-AP1 (p12DOC−1) expression in human colorectal cancer

Yuan, Ziquan; Gaba, Anu G.; Kent, Tara S.; Bennett, Anna; Miller, A.; Weber, Thomas K.

doi:10.1038/sj.onc.1208378

Cited by 12 publications

(11 citation statements)

References 28 publications

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“…It has recently been reported that p12 DOC-1 expression was associated with microsatellite status in human colorectal cancer. Its expression was significantly decreased in microsatellite-unstable cell lines, but not in microsatellite-stable cell lines, and its loss was characterized by increased cell proliferation and decreased apoptosis [5,19,20] .…”

Section: Discussionmentioning

confidence: 99%

Decreased Expression of p12<sup>DOC-1</sup> Is Associated with More Advanced Tumor Invasion in Human Gastric Cancer Tissues

Choi¹,

Sohn²,

Park

et al. 2009

Eur Surg Res

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Background/Aims: p12^DOC-1 is a well-known growth suppressor; however, its role in gastric carcinogenesis is still unclear. We investigated the expression of p12^DOC-1 in gastric cancer tissues and its possible correlation with p53 expression, and determined its clinical significance. Methods: Immunohistochemical staining using the tissue array method was performed on 180 human gastric carcinomas. The clinicopathological features and prognostic significance were analyzed. Results: Of the 180 tissue samples, p53 expression was positive in 85 (47.2%) and p12^DOC-1 expression was negative in 140 (77.8%). The negative expression of p12^DOC-1 was significantly associated with a more advanced depth of tumor invasion and stage (p < 0.05). No apparent correlation was found between p12^DOC-1 and p53 expressions. The 5-year survival rate of the p12^DOC-1-positive cases (53.7%) was higher than that of the p12^DOC-1-negative cases (39.3%); however, neither p12^DOC-1 nor p53 expression status had any statistically significant prognostic value. Multivariate analysis revealed that lymph node metastasis, distant metastasis, lymphatic invasion and perineural invasion were independent prognostic factors. Conclusions: This is the first report that suggests that p12^DOC-1 may be involved in the development and progression of gastric cancer. Further studies are required to clarify its exact role in the mechanism of gastric carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Decreased Expression of p12<sup>DOC-1</sup> Is Associated with More Advanced Tumor Invasion in Human Gastric Cancer Tissues

Choi¹,

Sohn²,

Park

et al. 2009

Eur Surg Res

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“…Viral E6 oncoprotein has been shown to induce CIAP2 expression through either the NF-κB or EGFR/PI3K/AKT signaling pathways. CIAP2 confers less sensitivity to apoptosis in HPV16 E6-immortalized human oral keratinocytes (Yuan et al, 2005; James et al, 2006), and resistance to cisplatin in HPV-infected lung cancer (Wu et al, 2010), or 5-FU treatment of HNSCC cell lines (Nagata et al, 2011). Furthermore, high CIAP2 expression was associated with poor clinical outcome, at least in patients with oral squamous cell carcinoma (Nagata et al, 2011).…”

Section: Cell Intrinsic Features Of Hpv-positive Tumor Cellsmentioning

confidence: 99%

New Concepts for Translational Head and Neck Oncology: Lessons from HPV-Related Oropharyngeal Squamous Cell Carcinomas

2012

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Human papillomavirus (HPV) infection is well established as an etiological agent responsible for a number of pathologies affecting the stratified epithelia of skin and anogenital sites. More recently, the infection by (mucosal) high-risk HPV types has also been found to be causally associated with squamous cell carcinoma in the head and neck region (HNSCC), especially in the oropharynx. Intriguingly, HPV-related oropharyngeal squamous cell carcinomas (OPSCC) represent a distinct clinical entity compared to HPV-negative tumors with particular regard to treatment–response and survival outcome. The association between HPV infection and OPSCC may therefore have important implications for the prevention and/or treatment of OPSCC. The improved survival of patients with HPV-related tumors also raises the question, as to whether a better understanding of the underlying differences may help to identify new therapeutic concepts that could be used in targeted therapy for HPV-negative and improved therapy for HPV-positive cancers. This review summarizes the most recent advances in our understanding of the molecular principles of HPV-related OPSCC, mainly based on functional genomic approaches, but also emphasizes the significant role played by the tumor microenvironment, especially the immune system, for improved clinical outcome and differential sensitivity of HPV-related tumors to current treatment options.

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“…However, RNAi-mediated CDK2AP1 inhibition is associated with decreased apoptosis and increased cell proliferation in colorectal cancer. 22 These controversial results in different cancer types reflect the complicated functions of CDK2AP1 in biological progression of different cancers. It was reported that mutation of Cys105 is essential to its growth suppressor effect in normal diploid cells, and the reduction of CDK2AP1 expression resulted in a parallel reduction of p25 that encodes a neuron-specific activator of cyclindependent kinase 5 (CDK5).…”

Section: Discussionmentioning

confidence: 99%

“…It is a partner of CDK2 and participates in cell-cycle regulation, apoptosis and proliferation. CDK2AP1 gene is usually expressed in normal human tissues, yet it is expressed at a higher level or lost in many types of cancers including head and neck squamous cell carcinoma, 16 oral cancer, 17 prostate cancer, 18 nasopharyngeal carcinoma, 19 esophageal carcinoma, 20 gastric cancer, 21 and colorectal cancer 22 . However, the precise role of CDK2AP1 in human glioma is still obscure.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of CDK2AP1 by RNA interference inhibits cell growth and tumorigenesis of human glioma

Wang

et al. 2013

Neurological Research

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Previous reports support the role of cyclin-dependent kinase 2-associated protein 1 (CDK2AP1) as a tumor suppressor that functions as a key player in cell cycle regulation. Although the misadjustment of CDK2AP1 has been revealed in several types of human malignancies, the functional role of CDK2AP1 in human glioma remains unknown. The present study was undertaken to investigate the effects of CDK2AP1 knockdown by RNA interference (RNAi) on glioma cell growth and tumorigenesis. We employed lentivirus-mediated RNAi to down-regulate CDK2AP1 expression in U251 and U373 cells. Knockdown of CDK2AP1 resulted in a significant reduction in U251 and U373 cell proliferation, as determined by MTT and colony formation assays. Cell cycle analysis showed CDK2AP1 silencing caused U251 cells arrest in G0/G1 phase, especially in the sub-G1 phase representing apoptotic cells. In vivo tumorigenesis was assessed using xenograft formation and CDK2AP1 depletion remarkably inhibited glioma growth and tumorigenesis. Taken together, these results suggest that CDK2AP1 siRNA may have an anti-tumorigenic effect on human glioma.

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Modulation of CDK2-AP1 (p12DOC−1) expression in human colorectal cancer

Cited by 12 publications

References 28 publications

Decreased Expression of p12<sup>DOC-1</sup> Is Associated with More Advanced Tumor Invasion in Human Gastric Cancer Tissues

Decreased Expression of p12<sup>DOC-1</sup> Is Associated with More Advanced Tumor Invasion in Human Gastric Cancer Tissues

New Concepts for Translational Head and Neck Oncology: Lessons from HPV-Related Oropharyngeal Squamous Cell Carcinomas

Knockdown of CDK2AP1 by RNA interference inhibits cell growth and tumorigenesis of human glioma

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