Journal Club: Circadian homeostasis and tumorigenesis

Understanding the basis and treatment of disease.

Moderators: Calilasseia, ADParker

Journal Club: Circadian homeostasis and tumorigenesis

#1  Postby natselrox » Aug 03, 2010 1:48 pm

GenesForLife recommended this one for this month's Journal Club. I have read the article and would love to discuss it and the various aspects of Chronobiology in general.

The whole article can be found at: http://www.plosone.org/article/info:doi ... 5-Reppert1

Abstract

Background
Cell proliferation in all rapidly renewing mammalian tissues follows a circadian rhythm that is often disrupted in advanced-stage tumors. Epidemiologic studies have revealed a clear link between disruption of circadian rhythms and cancer development in humans. Mice lacking the circadian genes Period1 and 2 (Per) or Cryptochrome1 and 2 (Cry) are deficient in cell cycle regulation and Per2 mutant mice are cancer-prone. However, it remains unclear how circadian rhythm in cell proliferation is generated in vivo and why disruption of circadian rhythm may lead to tumorigenesis.

Methodology/Principal Findings
Mice lacking Per1 and 2, Cry1 and 2, or one copy of Bmal1, all show increased spontaneous and radiation-induced tumor development. The neoplastic growth of Per-mutant somatic cells is not controlled cell-autonomously but is dependent upon extracellular mitogenic signals. Among the circadian output pathways, the rhythmic sympathetic signaling plays a key role in the central-peripheral timing mechanism that simultaneously activates the cell cycle clock via AP1-controlled Myc induction and p53 via peripheral clock-controlled ATM activation. Jet-lag promptly desynchronizes the central clock-SNS-peripheral clock axis, abolishes the peripheral clock-dependent ATM activation, and activates myc oncogenic potential, leading to tumor development in the same organ systems in wild-type and circadian gene-mutant mice.

Conclusions/Significance
Tumor suppression in vivo is a clock-controlled physiological function. The central circadian clock paces extracellular mitogenic signals that drive peripheral clock-controlled expression of key cell cycle and tumor suppressor genes to generate a circadian rhythm in cell proliferation. Frequent disruption of circadian rhythm is an important tumor promoting factor.


For those without a basic introduction to Chronobio and circadian rhythms in general, I recommend this video. Actually, I recommend it for EVERYONE!

[youtube]http://www.youtube.com/watch?v=4McpjIiBlHI[/youtube]

I'd also like to recommend one of my favourite blogs: http://scienceblogs.com/clock/chronobiology/

Let's discuss! :cheers:
When in perplexity, read on.

"A system that values obedience over curiosity isn’t education and it definitely isn’t science"
User avatar
natselrox
THREAD STARTER
 
Posts: 10037
Age: 108
Male

India (in)
Print view this post

Ads by Google


Re: Journal Club: Circadian homeostasis and tumorigenesis

#2  Postby Darwinsbulldog » Aug 03, 2010 3:46 pm

Eeek! I need to do some reading here. Most of the genetics readings I do are on HOX.
Jayjay4547 wrote:
"When an animal carries a “branch” around as a defensive weapon, that branch is under natural selection".
Darwinsbulldog
 
Posts: 7440
Age: 65

Print view this post

Re: Journal Club: Circadian homeostasis and tumorigenesis

#3  Postby Oeditor » Aug 04, 2010 6:00 pm

Makes one wonder what the effects of thiotimoline might be!
The very reason food is sealed is to keep information out. - Gary Ablett Snr.
Oeditor
 
Posts: 4581
Male

United Kingdom (uk)
Print view this post

Re: Journal Club: Circadian homeostasis and tumorigenesis

#4  Postby GenesForLife » Sep 24, 2010 3:11 pm

Oeditor wrote:Makes one wonder what the effects of thiotimoline might be!


Apply for funding mate, let's find out.
GenesForLife
 
Posts: 2920
Age: 31
Male

United Kingdom (uk)
Print view this post

Re: Journal Club: Circadian homeostasis and tumorigenesis

#5  Postby natselrox » Sep 24, 2010 3:14 pm

GenesForLife wrote:
Oeditor wrote:Makes one wonder what the effects of thiotimoline might be!


Apply for funding mate, let's find out.


:rofl:
When in perplexity, read on.

"A system that values obedience over curiosity isn’t education and it definitely isn’t science"
User avatar
natselrox
THREAD STARTER
 
Posts: 10037
Age: 108
Male

India (in)
Print view this post



Return to Medicine

Who is online

Users viewing this topic: No registered users and 1 guest