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Microarray analysis of MYC-mediated death response pathways
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analytically, that is, calculating the changing levels of concentrations, for example, requires numerical simulations. For this, the authors used Virtual Cell (http://www.nrcam.uchc.edu/), which aims to provide an easy-to-use, intuitive modeling environment for biologists with little interest in computational processes. The success of Smith and colleagues was ensured by choosing a subcellular
TRENDS in Pharmacological Sciences Vol.23 No.4 April 2002
network that is almost completely described, robust and nearly functions as a module. Consequently, their experimental measurements, most convincingly the perturbation studies involving sharply decreasing Ran exchange factor (RCC1) concentrations, were closely matched by the calculated results. This has enabled the authors to produce experimentally testable and biologically
159
relevant predictions. The immediate future of systems biology seems to be ensured: biologists cannot back out of the game any more. 1 Smith, A.E. et al. (2001) Systems analysis of ran transport. Science 295, 488–491
Zoltan Szallasi [email protected]
Microarray analysis of MYC-mediated death response pathways The proto-oncogene MYC plays an important role in the control of proliferation, differentiation and apoptosis and its aberrant expression is commonly found in human cancers. Very little is known about genes involved in MYC pro-apoptotic functions. A recent study set out to identify the role of MYC in DNA-damage-mediated apoptosis, by comparing gene expression profiles of wild-type and MYC-null cells after DNA damage by VP16. Yu et al. [1] identified two gene clusters that were associated with VP16-induced apoptosis. Of these two, only one, which includes c-JUN, was highly regulated by MYC and appeared to be crucial for the maximal apoptotic response in wild-type
cells. The authors show that MYC levels dropped sharply following VP16 exposure, resulting in induction of genes of the MYC-responsive cluster. They conclude that removal of MYC-mediated repression of apoptotic signals is part of the mechanism by which MYC mediates a complete and rapid cell death following DNA damage. The implication of this conclusion is that any cell that has low MYC levels would therefore be more prone to undergo apoptosis. This seems to be in contrast with the biological notion that MYC sensitizes cells to undergo apoptosis simultaneously with cell proliferation, thus ensuing that only cells without any defect and in the right
environment are allowed to divide, whereas cells that encountered DNA damage or lack trophic support as a result of being in the wrong environment, will die by apoptosis. It will therefore be very interesting to see if the genes identified as cluster C in this study play a role in MYC sensitization to different pro-apoptotic triggers, such as serum deprivation and death receptor signaling.
ImClone Systems under scrutiny
UK researchers are the ‘poor relations’
The FDA’s rejection of ImClone Systems’ anticancer drug Erbitux has given rise to intense public speculation about the company’s clinical trials and business practices. According to some reports, ImClone disregarded the FDA’s request for better documentation of the claim that the patients enrolled in the pivotal clinical trial were truly resistant to traditional chemotherapy. A congressional committee launched an investigation in mid-January 2002 to investigate whether the company provided accurate information to its investors. The committee has also requested Bristol Myers Squibb, which invested US$1 billion in ImClone last year, to provide the names of people who conducted due diligence on ImClone, as well as copies of internal audits. AB
If the successful results of the UK’s 2001 Research Assessment Exercise served to inflate morale of researchers in the UK, the findings of a recent survey of academic pay might let the wind out of their sails. Conducted by the lecturers’ union in the UK, NATFHE, the survey showed that the average pay of UK academics was £21 800, a paltry sum compared with researchers in Canada who topped the list at £72 700, followed by those in Italy (£72 400) and the USA (£56 100). The values do not represent salary per se, but are an indicator of purchasing power that takes into account
taxes, benefits, cost of living and exchange rates. Because the findings are based on 1998 figures, one would hope that the situation for British researchers has improved since then, particularly as the UK government has pledged £830m for 2001–2004 specifically for the purpose of raising academic pay. DC
1 Yu, Q. et al. (2002) Identification of Mycmediated death response pathways by micro array analysis. J. Biol. Chem. 10.1074/jbc.M111403200
Marieke Kruidering [email protected]
In Brief
http://tips.trends.com
Receptors for relaxin found The peptide hormone relaxin has binding sites throughout the reproductive tract, in the heart and in the brain, but its receptor was unknown. Now, a new study identifies two orphan Gs-coupled receptors, LGR7 and LGR8, as the receptors for this hormone. In vivo administration of the purified soluble ectodomain of LGR7 to pregnant mice led to a delayed parturition, confirming a role of the hormone in the regulation of normal labour. [Hsu, S-Y. et al. (2002) Science 295, 671–674] AB
0165-6147/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.
analytically, that is, calculating the changing levels of concentrations, for example, requires numerical simulations. For this, the authors used Virtual Cell (http://www.nrcam.uchc.edu/), which aims to provide an easy-to-use, intuitive modeling environment for biologists with little interest in computational processes. The success of Smith and colleagues was ensured by choosing a subcellular
TRENDS in Pharmacological Sciences Vol.23 No.4 April 2002
network that is almost completely described, robust and nearly functions as a module. Consequently, their experimental measurements, most convincingly the perturbation studies involving sharply decreasing Ran exchange factor (RCC1) concentrations, were closely matched by the calculated results. This has enabled the authors to produce experimentally testable and biologically
159
relevant predictions. The immediate future of systems biology seems to be ensured: biologists cannot back out of the game any more. 1 Smith, A.E. et al. (2001) Systems analysis of ran transport. Science 295, 488–491
Zoltan Szallasi [email protected]
Microarray analysis of MYC-mediated death response pathways The proto-oncogene MYC plays an important role in the control of proliferation, differentiation and apoptosis and its aberrant expression is commonly found in human cancers. Very little is known about genes involved in MYC pro-apoptotic functions. A recent study set out to identify the role of MYC in DNA-damage-mediated apoptosis, by comparing gene expression profiles of wild-type and MYC-null cells after DNA damage by VP16. Yu et al. [1] identified two gene clusters that were associated with VP16-induced apoptosis. Of these two, only one, which includes c-JUN, was highly regulated by MYC and appeared to be crucial for the maximal apoptotic response in wild-type
cells. The authors show that MYC levels dropped sharply following VP16 exposure, resulting in induction of genes of the MYC-responsive cluster. They conclude that removal of MYC-mediated repression of apoptotic signals is part of the mechanism by which MYC mediates a complete and rapid cell death following DNA damage. The implication of this conclusion is that any cell that has low MYC levels would therefore be more prone to undergo apoptosis. This seems to be in contrast with the biological notion that MYC sensitizes cells to undergo apoptosis simultaneously with cell proliferation, thus ensuing that only cells without any defect and in the right
environment are allowed to divide, whereas cells that encountered DNA damage or lack trophic support as a result of being in the wrong environment, will die by apoptosis. It will therefore be very interesting to see if the genes identified as cluster C in this study play a role in MYC sensitization to different pro-apoptotic triggers, such as serum deprivation and death receptor signaling.
ImClone Systems under scrutiny
UK researchers are the ‘poor relations’
The FDA’s rejection of ImClone Systems’ anticancer drug Erbitux has given rise to intense public speculation about the company’s clinical trials and business practices. According to some reports, ImClone disregarded the FDA’s request for better documentation of the claim that the patients enrolled in the pivotal clinical trial were truly resistant to traditional chemotherapy. A congressional committee launched an investigation in mid-January 2002 to investigate whether the company provided accurate information to its investors. The committee has also requested Bristol Myers Squibb, which invested US$1 billion in ImClone last year, to provide the names of people who conducted due diligence on ImClone, as well as copies of internal audits. AB
If the successful results of the UK’s 2001 Research Assessment Exercise served to inflate morale of researchers in the UK, the findings of a recent survey of academic pay might let the wind out of their sails. Conducted by the lecturers’ union in the UK, NATFHE, the survey showed that the average pay of UK academics was £21 800, a paltry sum compared with researchers in Canada who topped the list at £72 700, followed by those in Italy (£72 400) and the USA (£56 100). The values do not represent salary per se, but are an indicator of purchasing power that takes into account
taxes, benefits, cost of living and exchange rates. Because the findings are based on 1998 figures, one would hope that the situation for British researchers has improved since then, particularly as the UK government has pledged £830m for 2001–2004 specifically for the purpose of raising academic pay. DC
1 Yu, Q. et al. (2002) Identification of Mycmediated death response pathways by micro array analysis. J. Biol. Chem. 10.1074/jbc.M111403200
Marieke Kruidering [email protected]
In Brief
http://tips.trends.com
Receptors for relaxin found The peptide hormone relaxin has binding sites throughout the reproductive tract, in the heart and in the brain, but its receptor was unknown. Now, a new study identifies two orphan Gs-coupled receptors, LGR7 and LGR8, as the receptors for this hormone. In vivo administration of the purified soluble ectodomain of LGR7 to pregnant mice led to a delayed parturition, confirming a role of the hormone in the regulation of normal labour. [Hsu, S-Y. et al. (2002) Science 295, 671–674] AB
0165-6147/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved.