Role of cell‐cycle regulators in lung cancer

Caputi, M; Russo, Giuseppe; Esposito, Vincenzo; Mancini, Alessandro; Giordano, Antonio

doi:10.1002/jcp.20424

Cited by 29 publications

(20 citation statements)

References 81 publications

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“…In this study, the effects of aerosol-delivered PDCD4 on cell cycle control in lungs of K-ras null mice were investigated. Initiation of cell cycle control via extracellular signals induces the transcription of several proteins, including cyclin D, which, when complexed with cyclin-dependent kinase 4, moves into the next cell cycle (30). In our study, aerosol-delivered PDCD4 may regulate lung cancer growth through increasing the cell cycle inhibitors, such as p21 and p27, while suppressing cell proliferation proteins, such as cyclindependent kinase 4 and proliferating cell nuclear antigen (Fig.…”

Section: Discussionmentioning

confidence: 91%

“…Interestingly, the effect of aerosol-delivered PDCD4 on p53 was insignificant. However, cell growth may be regulated by p53 target gene p21 because some research reports showed that p53 could bind to specific DNA sequence and transactivate a group of target genes, including p21, thereby inhibiting cell proliferation and promoting apoptosis (30).…”

Section: Discussionmentioning

confidence: 99%

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Aerosol delivery of urocanic acid–modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice

Jin

Kim

Hwang³

et al. 2006

Molecular Cancer Therapeutics

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The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for development of novel treatment options. Although several genes have been investigated for their antitumor activities through gene delivery, problems surrounding the methods used, such as efficiency, specificity, and toxicity, hinder application of such therapies in clinical settings.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Aerosol delivery of urocanic acid–modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice

Jin

Kim

Hwang³

et al. 2006

Molecular Cancer Therapeutics

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“…This is also due to the initial observations suggesting that RB family proteins have overlapping functions. However, several studies have evidenced functional differences among these proteins (Claudio et al, 1994;Hurford et al, 1997;Jori et al, 2004;Caputi et al, 2005). In this review, we will focus only the differences in regulation of stem cell biology.…”

Section: Rb and Hematopoiesismentioning

confidence: 99%

The retinoblastoma gene is involved in multiple aspects of stem cell biology

2006

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Genetic programs controlling self-renewal and multipotentiality of stem cells have overlapping pathways with cell cycle regulation. Components of cell cycle machinery can play a key role in regulating stem cell self-renewal, proliferation, differentiation and aging. Among the negative regulators of cell cycle progression, the RB family members play a prominent role in controlling several aspects of stem cell biology. Stem cells contribute to tissue homeostasis and must have molecular mechanisms that prevent senescence and hold 'stemness'. RB can induce senescence-associated changes in gene expression and its activity is downregulated in stem cells to preserve self-renewal. Several reports evidenced that RB could play a role in lineage specification of several types of stem cells. RB has a role in myogenesis as well as in cardiogenesis. These effects are not only related to its role in suppressing E2F-responsive genes but also to its ability to modulate the activity of tissue-specific transcription factors. RB is also involved in adipogenesis through a strict control of lineage commitment and differentiation of adipocytes as well in determining the switch between brown and white adipocytes. Also, hematopoietic progenitor cells utilize the RB pathway to modulate cell commitment and differentiation. In this review, we will also discuss the role of the other two RB family members: Rb2/p130 and p107 showing that they have both specific and overlapping functions with RB gene.

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“…Constitutive activation of cyclin E/cdk2 complexes has been often associated with G 1 /S deregulation and tumor progression (Harwell et al, 2004;Liao et al, 2004;Sunters et al, 2004). Among the target substrates that cdks phosphorylate are the members of the retinoblastoma (Rb) family proteins, which play a pivotal role as negative regulators of cell cycle progression (Claudio et al, 1994;Caputi et al, 2005;Gallo and Giordano, 2005). This family includes the product of the Rb susceptibility gene, the pRb/p105 protein and the related p107 and pRb2/130 proteins (Mayol et al, 1993;Du and Pogoriler, 2006;Merola et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

A small molecule based on the pRb2/p130 spacer domain leads to inhibition of cdk2 activity, cell cycle arrest and tumor growth reduction in vivo

et al. 2006

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One strategy in the development of anticancer therapeutics has been to arrest malignant proliferation through inhibition of the enzymatic activity of cyclin-dependent kinases (cdks), which are key regulatory molecules of the cell cycle. Over the past few years, numerous compounds with remarkable cdk inhibitory activity have been studied in cancer therapy, although it is very difficult to point out the best cdk to target. An excellent candidate appears to be cdk2, whose alteration is a pathogenic hallmark of tumorigenesis. The small molecule described in our study showed an inhibitory effect on the kinase activity of cdk2, a significant growth arrest observed in a colony formation assay and a reduction in the size of the tumor in nude mice, thus suggesting its potential role as a promising new type of mechanism-based antitumor drug, also for the treatment of hyperproliferative disorders.

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Role of cell‐cycle regulators in lung cancer

Cited by 29 publications

References 81 publications

Aerosol delivery of urocanic acid–modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice

Aerosol delivery of urocanic acid–modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice

The retinoblastoma gene is involved in multiple aspects of stem cell biology

A small molecule based on the pRb2/p130 spacer domain leads to inhibition of cdk2 activity, cell cycle arrest and tumor growth reduction in vivo

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