Cyclin E in human cancers

Donnellan, Rory; Chetty, Runjan

doi:10.1096/fasebj.13.8.773

Cited by 201 publications

(165 citation statements)

References 99 publications

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“…Future study is needed to explore whether the other major downstream property of cyclin D1/CDK4, e.g. sequestering the CDK inhibitor p27 Kip1 to trigger cyclin E-initiated Rb-independent S phase entry (Geng et al, 1999;Perez-Roger et al, 1999;Donnellan and Chetty, 1999), is associated with novel tumorigenic mechanisms caused by ampli®ed PIK3CA in cervical cancer development. Not mutually exclusive are the possibilities that, in cervical tumorigenesis, increased PIK3CA and elevated PI 3-kinase activity contribute to other AKT-involved growth-promoting pathways or antiapoptotic signal.…”

Section: Resultsmentioning

confidence: 99%

PIK3CA as an oncogene in cervical cancer

et al. 2000

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Section: Resultsmentioning

confidence: 99%

PIK3CA as an oncogene in cervical cancer

et al. 2000

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“…However, preclinical experiments have shown that the pattern of genetic alterations might determine the success or the failure of such strategies. Overexpression of CycE, together with p27 downregulation, has been related to tumor progression and stage in a number of malignancies like breast, stomach and colorectal cancer, and osteosarcoma (summarized in Donnellan and Chetty 45 ). Moreover, its prognostic value has been described in some of these cases.…”

Section: Discussionmentioning

confidence: 99%

The fate of pancreatic tumor cell lines following p16 overexpression depends on the modulation of CDK2 activity

et al. 2004

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Restitution of lost tumor-suppressor activities may be a promising strategy to target specifically cancer cells. However, the action of ectopically expressed tumor-suppressor genes depends on genetic background of tumoral cells. Ectopic expression of p16 INK4a induces either cell cycle arrest or apoptosis in different pancreatic cancer cell lines. We examined the molecular mechanisms mediating these two different cellular responses to p16 overexpression. Ectopic expression of p16 leads to G1 arrest in NP-9 cells by redistributing p21/p27 CKIs and inhibiting cyclin-dependent kinase CDK2 activity. In contrast, in NP-18 cells cyclin E (CycE)/ CDK2 activity is significantly higher and is not downregulated by p16-mediated redistribution of p21/p27. Moreover, inhibition of CDK4 activity with fascaplysine, which does not affect CycE/ CDK2 activity, reduces pocket protein phosphorylation in both cell lines, but fails to induce growth arrest. Like overexpression of p16, fascaplysine induces apoptosis in NP-18 cells, suggesting that inhibition of D-type cyclin/CDK activity in cells with high levels of CycE/CDK2 activity activates an apoptotic pathway. Inhibition of CycE/CDK2 activity via ectopic expression of p21 in NP-18 cells overexpressing p16 induces growth arrest and prevents p16-mediated apoptosis. Accordingly, silencing of p21 expression by using small interfering RNA switches the fate of p16-expressing NP-9 cells from cell cycle arrest to apoptosis. Our data suggest that, after CDK4/6 inactivation, the fate of pancreatic tumor cells depends on the ability to modulate CDK2 activity.

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“…In general, we observed parallel expression of Cdk2 with cyclin E, supporting the expected interaction of these two regulators as a complex. Overexpression of cyclin E has been reported in a variety of malignancies, including squamous cell carcinomas of lung and cervix, acute lymphoblastic leukemia, and in gastric adenocarcinoma, especially in deeply invasive tumors (32)(33)(34)(35)(36)(37). Our findings support an important role for cyclin E in the development of GTD, including choriocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Expression of Cell Cycle Proteins E2F-1, Cdk-2, Cyclin E, p27kip1, and Ki-67 in Normal Placenta and Gestational Trophoblastic Disease

et al. 2001

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The role of cell cycle protein expression in gestational trophoblastic disease is poorly understood. In this study we investigated the immunostaining patterns of G 1 restriction point and G 1 -S regulatory proteins E2F-1, Cdk2, cyclin E, p27 kip1 , and the proliferation marker Ki-67 on routinely processed sections of 29 hydatidiform moles (10 partial moles and 19 complete moles, including 9 persistent moles), 7 choriocarcinomas, and 7 normal placentas. Ki-67 trophoblast staining decreased with increasing gestational age of the placenta, and showed maximal expression in gestational trophoblastic disease. Cyclin-dependent kinase activity, as reflected by Cdk2 expression patterns, also decreased with placental maturation. E2F-1 was uniquely expressed by trophoblasts of moles and choriocarcinoma. Cyclin E was maximally expressed by complete moles and choriocarcinomas, and showed an inverse relationship with the cyclin-dependent kinase inhibitor p27 kip1 . Abnormal trophoblastic proliferations may be mediated through interactions of Cdk-2, E2F-1, cyclin E, and p27 kip1 . Overexpression of cyclin E was associated with more aggressive forms of gestational trophoblastic disease. However, we did not find distinguishing features between complete moles that spontaneously resolved after evacuation and persistent moles that required chemotherapy. The different expression patterns of cyclin E and E2F-1 in partial and complete moles may be useful in distinguishing these two entities. Furthermore, loss of p27 kip1 in malignant trophoblast may represent a necessary step in the development of choriocarcinoma.KEY WORDS: Cdk2, Choriocarcinoma, Cyclin E, E2F-1, Ki-67, p27 kip1 , Trophoblast.Mod Pathol 2001;14(10)

show abstract

Cyclin E in human cancers

Cited by 201 publications

References 99 publications

PIK3CA as an oncogene in cervical cancer

PIK3CA as an oncogene in cervical cancer

The fate of pancreatic tumor cell lines following p16 overexpression depends on the modulation of CDK2 activity

Immunohistochemical Expression of Cell Cycle Proteins E2F-1, Cdk-2, Cyclin E, p27kip1, and Ki-67 in Normal Placenta and Gestational Trophoblastic Disease

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