Cell Cycle Control and Cancer

Hartwell, Leland H.; Kastan, Michael B.

doi:10.1126/science.7997877

Cited by 2,292 publications

(1,418 citation statements)

References 131 publications

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“…25,26 In particular, increasing evidence has clearly demonstrated that cancer transformation is due to the loss of function of specific tumor suppressor genes (Rb, p53, and p16 genes) controlling the cell division cycle in many tumors. 27 Tumors with chromosomal translocation, which is considered a main genetic lesion for the tumor, are often accompanied by additional aberration of tumor suppressor gene(s). 28,29 In our present study, a subset of acute leukemias with MLL gene rearrangement demonstrated homozygous deletion of p16 and p15 genes.…”

Section: Discussionmentioning

confidence: 99%

Alterations of p16 and p15 genes in acute leukemia with MLL gene rearrangements and their correlation with clinical features

et al. 1997

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p16 and p15 genes are putative tumor suppressor genes located on chromosome 9p21. In acute leukemias, alterations of p16 and p15 genes have been reported to occur exclusively in lymphoid lineage. We analyzed alterations of p16 and p15 genes in 46 acute leukemias with MLL gene rearrangements by Southern blot analysis, and investigated the association with clinical characteristics. We identified homozygous deletion of p16 and p15 genes in five (19%) of 27 acute lymphoblastic leukemias (ALLs) and in two (11%) of 19 acute myeloid leukemias (AMLs). Patients with homozygous deletion of p16 and p15 genes showed higher average leukocyte counts (343 × 10 9 /l vs 271 × 10 9 /l) and lower estimated 2-year survival rates than those with normal p16 and p15 genes (14.3 vs 30.7%), although the differences were not statistically significant. In addition, we investigated mutation of p16 gene by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) in 31 patients, but no mutation was found in the patients tested. Our results suggest that alterations of p16 and p15 genes are involved in a subset of acute leukemias with MLL gene rearrangement not only of lymphoid but also of myeloid phenotype. Homozygous deletion of p16 and p15 genes may be a possible adverse prognostic factor, although further analysis would be needed to confirm it.

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Section: Discussionmentioning

confidence: 99%

Alterations of p16 and p15 genes in acute leukemia with MLL gene rearrangements and their correlation with clinical features

et al. 1997

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“…All of these lesions have been shown to block transcription in vivo and in vitro, and to be implicated in signaling cell cycle arrest and apoptosis (Kulms and Schwarz, 2002). Cell survival after DNA damage is dependent on two important biological responses: the activation of cell cycle checkpoints and of DNA repair machinery (Hartwell and Kastan, 1994).…”

Section: Cell Cycle Checkpointsmentioning

confidence: 99%

Cell cycle control and beyond: emerging roles for the retinoblastoma gene family

et al. 2006

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Rb family proteins (pRb/p105, Rb2/p130 and p107) play a key role in cell cycle control and are worthily involved in transcription repression and tumor suppression. The mechanisms of transcriptional activation and repression by the Rb gene family has been extensively investigated: pRb, pRb2/p130 and p107 interact with different E2F family factors and can inhibit E2F responsive promoters, interfering with progression of cell cycle, gene transcription, initiation of apoptotic process and cell differentiation. Recent studies have indicated that Rb and Rb2/p130 may be involved in cellular response to DNA damage events, by influencing the transcription of factors involved in DNA repair pathways. In particular, evidences suggest that Rb loss and target gene deregulation impacts on the repair of UV-induced pyrimidine pyrimidone photoproducts (6-4 PP) by regulating the expression of several DNA damage factors involved in UV DNA damage repair processes, including proliferating cell nuclear antigen. Ongoing studies are focused on the mechanisms by which Rb family genes drive cell cycle exit following DNA damage induction, and how Rb gene family's interaction with chromatin remodeling factors can influence DNA repair dynamics.

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“…In an individual, however, if either of these processes is not regulated properly, the cell number can increase inappropriately to cause tumour formation (Hartwell and Kastan, 1994). During apoptosis, cells die by following an ordered intracellular mechanism in which proteins and DNA are degraded.…”

Section: Introductionmentioning

confidence: 99%

Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin treatment

et al. 2006

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We have studied the role of cyclins and cyclin-dependent kinase (CDK) activity in apoptosis induced by camptothecin (CPT). In this model, 22% of the cells stain for annexin-V at 24 h and then proceed to be 93% positive by 72 h. This time window permits the analysis of cyclins in cells that are committed to apoptosis but not yet dead. We provide evidence that cyclin protein levels and then associated kinase levels increase after CPT treatment. Strikingly, cyclin B1 and cyclin E1 proteins are present at the same time in CPT treated HT29 cells. Although cyclin B1 and E1 CDK complexes are activated in CPT treated cells, only the cyclin B1 complex is required for apoptosis since reduction of cyclin B1 by RNAi or roscovitine treatment reduces the number of annexin-V-stained cells. We have detected poorly organized chromosomes and phosphorylated histone H3 epitopes at the time of maximum cyclin B1/CDK kinase activity in CPT-treated cells, which suggests that these cells enter a mitotic catastrophe. Understanding which CDKs are required for apoptosis may allow us to better adapt CDK inhibitors for use as anti-cancer compounds.

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Cell Cycle Control and Cancer

Cited by 2,292 publications

References 131 publications

Alterations of p16 and p15 genes in acute leukemia with MLL gene rearrangements and their correlation with clinical features

Alterations of p16 and p15 genes in acute leukemia with MLL gene rearrangements and their correlation with clinical features

Cell cycle control and beyond: emerging roles for the retinoblastoma gene family

Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin treatment

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