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The lack of malignant tumors in mice expressing decreased levels of TSC1 or TSC2 is associated with decreased PDGFR expression and decreased PI3K and AKT activity, despite increased mTOR activity. Hongbing Zhang and colleagues now show that in mouse cell lines, activation of PI3K or AKT, as well as inhibition of PTEN, results in decreased PDGFR expression and negative feedback to dampen AKT activity, despite increased mTOR activity. Furthermore, inhibiting mTOR restored PDGFR expression levels and AKT activity in mouse cell lines expressing decreased levels of TSC1 or TSC2, and overexpression of active AKT or PDGFR in such cells rendered them able to induce malignant tumors when transplanted into immunocompromised mice. This study therefore demonstrates that increased mTOR activity decreases PDGFR expression and AKT activity in mouse cells expressing decreased levels of TSC1 or TSC2. More importantly, it offers a potential explanation for the observation that humans expressing mutant forms of TSC1 or TSC2 develop only benign tumors.

TITLE: PDGFRs are critical for PI3/Akt activation and negatively regulated by mTOR

AUTHOR CONTACT:
Hongbing Zhang
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Peoples Republic of China.
Phone: +86-10-6529-6945; Fax: +86-10-6529-6945; E-mail: hbzhang2006@gmail.com.

View the PDF of this article at: https://www.the-jci.org/article.php?id=28984