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Published on: September 11, 2013
Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways
1Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas, 75235-9040, USA.
Abstract:
The control of cell and organ growth is fundamental to the development of multicellular organisms. Here, we show that dPTEN, a Drosophila homolog of the mammalian PTEN tumor suppressor gene, plays an essential role in the control of cell size, cell number, and organ size. In mosaic animals, dPTEN(-) cells proliferate faster than their heterozygous siblings, show an autonomous increase in cell size, and form organs of increased size, whereas overexpression of dPTEN results in opposite phenotypes. The loss-of-function phenotypes of dPTEN are suppressed by mutations in the PI3K target Dakt1 and the translational initiation factor eif4A, suggesting that dPTEN acts through the PI3K signaling pathway to regulate translation. Although activation of PI3K and Akt has been reported to increase rates of cellular growth but not proliferation, loss of dPTEN stimulates both of these processes, suggesting that PTEN regulates overall growth through PI3K/Akt-dependent and -independent pathways. Furthermore, we show that dPTEN does not play a major role in cell survival during Drosophila development. Our results provide a potential explanation for the high frequency of PTEN mutation in human cancer.
Insights
Drosophila dPTEN, a tumor suppressor, controls cell and organ growth. Loss of dPTEN boosts cell proliferation and size, impacting organism development and potentially explaining PTEN mutations in human cancer.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Cell and organ growth control is crucial for multicellular organisms.
- PTEN (Phosphatase and tensin homolog) is a known tumor suppressor gene in mammals.
Purpose of the Study:
- To investigate the role of Drosophila dPTEN, a homolog of mammalian PTEN, in regulating cell and organ size.
- To elucidate the signaling pathways involved in dPTEN-mediated growth control.
Main Methods:
- Utilizing mosaic animals to observe the effects of dPTEN loss-of-function and overexpression.
- Genetic analysis involving mutations in PI3K (Phosphatidylinositol 3-kinase) pathway components like Dakt1 and translational factors like eif4A.
Main Results:
- Loss of dPTEN leads to increased cell proliferation, cell size, and organ size in Drosophila.
- Overexpression of dPTEN results in opposite phenotypes.
- dPTEN's function is linked to the PI3K signaling pathway, regulating translation.
- dPTEN influences both cell proliferation and growth, potentially through both PI3K/Akt-dependent and -independent pathways.
- dPTEN does not significantly impact cell survival during development.
Conclusions:
- Drosophila dPTEN is essential for controlling cell, cell number, and organ size.
- dPTEN functions via the PI3K signaling pathway to regulate translation and overall growth.
- These findings offer insights into the role of PTEN mutations in human cancers.
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