Table of Contents

Volume 2, Issue 1

  January/February 2003

  Pages 1 - 62

View covers archive

 Issue Catalogue (MARC XML)

PORTRAIT OF AN EDITORIAL BOARD MEMBER

Open Access Article

Martin Raff

Béatrice Durand and Valérie Wallace
Pages 1 - 2
http://dx.doi.org/10.4161/cc.2.1.184
Abstract | PDF

No abstract available




TRENDS IN SCIENCE

Open Access Article

Conceptual Research and Phenomenology

Mikhail V. Blagosklonny
Pages 3 - 4
http://dx.doi.org/10.4161/cc.2.1.220
Abstract | PDF

NA




RETROVIEW

Open Access Article

Oncogenic Potential of the c-FMS Proto-Oncogene (CSF-1 Receptor)

Martine F. Roussel and Charles J. Sherr
Pages 5 - 6
http://dx.doi.org/10.4161/cc.2.1.295
Abstract | PDF

A brief review of the paper:

Transforming Potential of the C-fms Proto-Oncogene (CFS-1 Receptor)

Roussel MF, Dull TJ, Rettenmier CW, Ralph P, Ullrich A, Sherr CJ.

Nature 1987 1987; 325: 549-552.




STORY OF DISCOVERY

Open Access Article

Redefining p53: Entering the Tumor Suppressor Era

Suzanne J. Baker
Pages 7 - 8
http://dx.doi.org/10.4161/cc.2.1.288
Abstract | PDF

no absract available




EXTRA VIEWS

Open Access Article

NF-κB Signaling: An ALternate Pathway for Oxidate Stress Responses

Peter Storz and Alex Toker
Pages 9 - 10
http://dx.doi.org/10.4161/cc.2.1.234
Abstract | PDF

NA

Open Access Article

Myc's Mastery of Mitochondrial Mischief

Fionnuala Morrish and David Hockenbery
Pages 11 - 13
http://dx.doi.org/10.4161/cc.2.1.275
Abstract | PDF

No abstract available

Open Access Article

Lethal Errors in Checkpoint Control: Life without Chk1

George Zachos, Michael Rainey and David A.F. Gillespie
Pages 14 - 16
http://dx.doi.org/10.4161/cc.2.1.277
Abstract | PDF

no abstract available

Open Access Article

Single-Strand DNA Gaps Trigger an ATR- and Cdc7-Dependent Checkpoint

Vincenzo Costanzo and Jean Gautier
Page 17
http://dx.doi.org/10.4161/cc.2.1.290
Abstract | PDF

No abstract available

Open Access Article

The Newly Identified Q Motif of DEAD Box Heicases IS Involved in Adenine Recognition

N. Kyle Tanner
Pages 18 - 19
http://dx.doi.org/10.4161/cc.2.1.296
Abstract | PDF

NA

Open Access Article

p53: Guardian of a Genome's Guardian?

Carlos P. Rubbi and Jo Milner
Pages 20 - 21
http://dx.doi.org/10.4161/cc.2.1.297
Abstract | PDF

NA




INFERENCES AND HYPOTHESES

Open Access Article

Cytotoxic Ribonucleases and RNA Interference (RNAi)

Barbara Ardelt, Wojciech Ardelt and Zbigniew Darzynkiewicz
Pages 22 - 24
http://dx.doi.org/10.4161/cc.2.1.232
Abstract | PDF

Several cytotoxic ribonucleases (CRs), homologs of the pancreatic RNase A, have been isolated from amphibian oocytes or embryos. Of them, onconase (Onc), the CR that shows antitumor properties and is in phase III clinical trials, was the most extensively researched. Degradation of tRNA by Onc internalized into cells that leads to inhibition of protein synthesis is considered the mechanism of its cytotoxicity. Several findings, however, cannot not be explained by nonspecific decline in protein synthesis alone and suggest additional or alternative mechanism(s). We postulate therefore that miRNAs and/or RNA interference (RNAi) may also be targets of CRs. The following arguments support this postulate: (A) miRNAs and siRNAs appear to be unprotected by proteins and therefore, as tRNA, accessible and degradable by CRs; (B) Onc has preferred cleavage sites on tRNAs: their cleavage may generate segments of dsRNA that interfere with translation. Analogous to Dicer, thus, small RNAs with interfering properties may be generated by CRs within the cell; (c) CRs are abundant in oocytes and during embryonic development; their role there is unknown. Since cells undergo perpetual differentiation during embryogenesis it is likely that the function of CRs is to provide additional level of regulation of gene expression via the mechanisms listed in (A) and/or (B).




VIEWS AND COMMENTARIES

Open Access Article

An Epigenetic Approach for Finding Tumor Suppressors

Peter A. Jones
Pages 25 - 26
http://dx.doi.org/10.4161/cc.2.1.251
Abstract | PDF

No abstract available

Open Access Article

Alternative Reading Frame Supports An Alternative Model for Retinoblastoma

Eldad Zacksenhaus
Pages 27 - 30
http://dx.doi.org/10.4161/cc.2.1.252
Abstract | PDF

The recent observation by Tyler Jacks' group that loss of ARF accelerates pituitary tumors in Rb+/-:Arf-/- mice by inducing proliferation without affecting apoptosis allows one to speculate about an alternative model for retinoblastoma. Retinoblasts in human and pituitary gland melanotrophs in the mouse might be uniquely susceptible to bi-allelic inactivation of Rb because upon loss-of-heterozygosity, these tissues are able to slowly proliferate without effectively activating the cell death machinery, and respond to an additional oncogenic signal. But what is the nature of this proliferation-permissive oncogenic alteration?

Open Access Article

More Than One Road to Kill Tumor Cells: Why Are They Not Always Successful?

Boris Zhivotovsky
Pages 31 - 33
http://dx.doi.org/10.4161/cc.2.1.253
Abstract | PDF

No Abstract Available

Open Access Article

Epigenetics is Back! HSP90 and Phenotypic Variation

Massimo Pigliucci
Pages 34 - 35
http://dx.doi.org/10.4161/cc.2.1.274
Abstract | PDF

No abstract available

Open Access Article

The Way to the End Matters: The Role of Telomerase in Tumor Progression

Alison A. Bertuch, Kathleen Buckley and Victoria Lundblad
Pages 36 - 38
http://dx.doi.org/10.4161/cc.2.1.278
Abstract | PDF

No Abstract Available

Open Access Article

G2 Cell Cycle Arrest: A Direct Link Between PKA and Cdc25C

Ellen K. Shibuya
Pages 39 - 41
http://dx.doi.org/10.4161/cc.2.1.291
Abstract | PDF

No abstract available




REPORTS

Open Access Article

Synchrony in Human, Mouse and Bacterial Cell Cultures: A Comparison

Charles E. Helmstetter, Maureen Thornton, Ana Romero and K. Leigh Eward
Pages 42 - 45
http://dx.doi.org/10.4161/cc.2.1.185
Abstract | PDF

Growth characteristics of synchronous human MOLT-4, human U-937 and mouse L1210 cultures produced with a new minimally-disturbing technology were compared to each other and to synchronous Escherichia coli B/r. Based on measurements of cell concentrations during synchronous growth, synchrony persisted in similar fashion for all cells. Cell size and DNA distributions in the mammalian cultures also progressed synchronously and reproducibly for multiple cell cycles. The results demonstrate that unambiguous multi-cycle synchrony, critical for verifying the absence of significant growth imbalances induced by the synchronization procedure, is feasible with these cell lines, and possibly others.

Open Access Article

Theoretical and Experimental Evidence for Hysteresis in Cell Proliferation

Shaochun Bai, David Goodrich, C. Dennis Thron, Edwin Tecarro and Mandri Obeyesekere
Pages 46 - 51
http://dx.doi.org/10.4161/cc.2.1.186
Abstract | PDF

We propose a mathematical model for the regulation of the G1-phase of the mammalian cell cycle taking into account interactions of cyclin D/cdk4, cyclin E/cdk2, Rb and E2F. Mathematical analysis of this model As a predicts that a change in the proliferative status in response to a change in concentrations of serum growth factors will exhibit the property of hysteresis: the concentration of growth factors required to induce proliferation is higher than the concentration required to maintain proliferation. We experimentally confirmed this prediction in mouse embryonic fibroblasts in vitro. In agreement with the mathematical model, this indicates that changes in proliferative mode caused by small changes in concentrations of growth factors are not easily reversible. Based on this study, we discuss the importance of proliferation hysteresis for cell cycle regulation.

Open Access Article

Leukemic and Non-Leukemic Lymphocytes from Patients with Li Fraumeni Syndrome Demonstrate Loss of p53 Function, Bcl-2 Family Dysregulation and Intrinsic Resistance to Conventional Chemotherapeutic Drugs But Not Flavopiridol

Chris Pepper, Alun Thomas, Terry Hoy, Jane Tighe, Dominic Culligan, Chris Fegan and Paul Bentley
Pages 52 - 57
http://dx.doi.org/10.4161/cc.2.1.249
Abstract | PDF

Li Fraumeni syndrome (LFS) is characterised by a predisposition to the early onset of certain tumors and is associated with germline mutation of the anti-oncogene p53. In this study we analysed the in vitro responses of lymphocytes from two LFS patients to chemotherapeutic drugs in terms of apoptosis induction and the expression of key intracellular proteins that regulate this process. One of the LFS patients also suffered from B-cell chronic lymphocytic leukemia (B-CLL) and hence presented with a light-chain restricted B-cell lymphocytosis while the other patient had entirely normal blood counts. The B-lymphocytes from both LFS patients showed a marked degree of resistance to chlorambucil and fludarabine when compared to age-matched controls but were remarkably sensitive to the novel flavone, flavopiridol. Loss of function of p53 was demonstrated by a failure to induce Bax and p21 protein expression. In addition, altered basal expression patterns of Bcl-2 and Bax, two key regulators of apoptosis, were found in the LFS lymphocytes when compared with controls. These results suggest that LFS lymphocytes carrying a p53 mutation show intrinsic resistance to conventional chemotherapeutic drugs and this is associated with dysregulation of Bcl-2 family proteins. Furthermore, The innate resistance profile was similar in leukemic and non-leukemic lymphocytes and was therefore independent of genetic changes acquired during malignant transformation. Novel agents that induce p53-independent cell killing may be useful not only in the treatment of LFS-associated tumors but also drug resistant tumors in general where p53 and/or Bcl-2 family dysregulation is a feature.

Open Access Article

PC-SPES Inhibits Cell Proliferation by Modulating p21, Cyclins D, E and B and Multiple Cell Cycle-Related Genes in Prostate Cancer Cells

Xiaohua Lu, Junqiao Guo and Tze-chen Hsieh
Pages 58 - 62
http://dx.doi.org/10.4161/cc.2.1.273
Abstract | PDF

PC-SPES is an herbal mixture, with evidence of clinical efficacy against prostate cancer (CaP), recently attracting tremendous attention. Using immunoblot and cell cycle specific cDNA array analyses, we investigated effects of PC-SPES on LNCaP, a hormone-dependent prostate cancer cell line. PC-SPES inhibited expression of cyclins D and E, inhibited Rb phosphorylation, switching it to a G1-to-S inhibitory state. Moreover, cDNA array analysis showed that PC-SPES caused up-regulation of p21WAF1/CIP1 and decreased expression of cyclin B, Nedd8, cdc2, skp1, PCNA, MAD2L1, cyclin H, CKS2, E2F, Rbx1, MCM2, MCM5, Mpp2, Cullin-Cul4A, Cks1p9 and McM7, which are involved in cell cycle progression. Taken together, our results provide a mechanistic explanation for antiproliferative and antitumor effects of PC-SPES, suggesting that induction of CDK inhibitors and downregulation of cyclins leads to dephosphorylation of Rb and growth arrest.