Requirement for cyclin D3 in lymphocyte development and T cell leukemias

Sicińska, Ewa; Aifantis, Iannis; Cam, Laurent Le; Swat, Wojciech; Borowski, Christine; Yu, Qunyan; Ferrando, Adolfo A.; Levin, Steven D.; Geng, Yan; Boehmer, Harald von; Siciński, Piotr

doi:10.1016/s1535-6108(03)00301-5

Cited by 306 publications

(355 citation statements)

References 51 publications

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“…Cyclin D3 was also found overexpressed in several human cancers (Ito et al, 2001;Wong et al, 2001;Hedberg et al, 2002;Pruneri et al, 2005) such as malignancies of the thymus (Filipits et al, 2002). Consistent with these results Sicinska et al (2003) established that cyclin D3-deficient mice displayed specific defects in the development of T lymphocytes. In addition to their growth-promoting functions, it was suggested that cyclin D3 plays a unique, nonredundant tissue-specific role such as in muscle differentiation (Kiess et al, 1995;Mariappan and Parnaik, 2005).…”

Section: Introductionsupporting

confidence: 82%

Cyclin D2 and cyclin D3 play opposite roles in mouse skin carcinogenesis

Rojas¹,

Cadenas

Lin

et al. 2006

Oncogene

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D-type cyclins are components of the cell-cycle engine that link cell signaling pathways and passage throughout G1 phase. We previously described the effects of overexpression cyclin D1, D2 or D3 in mouse epidermis and tumor development. We now asked whether cyclin D2 and/or cyclin D3 play a relevant role in ras-dependent tumorigenesis. Here, we described the effect of cyclin D3 and cyclin D2 overexpression in mouse skin tumor development. Notably, overexpression of cyclin D3 results in reduced tumor development and malignant progression to squamous cell carcinomas (SCC). Biochemical analysis of keratinocytes shows that overexpression of cyclin D3 results in strong reduction of cyclin D2 and its associated kinase activity. Furthermore, we found that reinstatement of cyclin D2 level in the cyclin D3/cyclin D2 bigenic mice results in a complete reversion of the inhibitory action of cyclin D3. Supporting these results, ablation of cyclin D2 results in reduced tumorigenesis and malignant progression. On the other hand, overexpression of cyclin D2 results in an increased number of papillomas and malignant progression. We conclude that cyclin D3 and cyclin D2 play opposite roles in mouse skin tumor development and that the suppressive activity of cyclin D3 is associated with cyclin D2 downregulation.

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Section: Introductionsupporting

confidence: 82%

Cyclin D2 and cyclin D3 play opposite roles in mouse skin carcinogenesis

Rojas¹,

Cadenas

Lin

et al. 2006

Oncogene

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“…39 Reinforcing this idea, CycE1 and CycE2 double knockout mice are also viable and show no major developmental problems. 40,41 However, minor cell cycle aberrations observed in cultured embryonic fibroblasts from these mice (CDK2KO, CycE1/E2DKO) seem to indicate an increased sensitivity to antiproliferative signaling during G1 phase, as they enter senescence earlier and show increased resistance to oncogene-induced transformation. Results presented here demonstrate that cell cycle arrest following p16 overexpression depends on the relative levels of cyclin/CDK2 complexes and p21/p27, suggesting a prevalence of CDK2 activity in the control of cell cycle progression.…”

Section: Discussionmentioning

confidence: 96%

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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“…Notch directly regulates D-type cyclins, which, in conjunction with cyclin-dependent kinase (cdk) 4 and cdk6 facilitate progression through the G 1 phase (Ronchini and Capobianco, 2000). In fact, in vitro and in vivo experiments indicate that upregulation of D-type cyclins is required for Notch-mediated transformation (Sicinska et al, 2003;Stahl et al, 2006). p27 is a cdk inhibitor that sequesters cyclin E to prevent cdk2 activation and S-phase progression (reviewed in Sherr and Roberts, 1999).…”

Section: Notch Regulates Cell-cycle Progressionmentioning

confidence: 99%