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Cowden syndrome-associated germline SDHD variants alter PTEN nuclear translocation through SRC-induced PTEN oxidation.

Yu W, He X, Ni Y, Ngeow J, Eng C - Hum. Mol. Genet. (2014)

Bottom Line: However, very little is known about the underlying crosstalk between SDHD and PTEN in CS-associated thyroid cancer.We show that SRC inhibition could rescue SDHD dysfunction-induced cellular phenotype and tumorigenesis only when wild-type PTEN is expressed, in thyroid cancer lines.Patient lymphoblast cells carrying either SDHD-G12S or SDHD-H50R also show increased nuclear PTEN and more oxidized PTEN after hydrogen peroxide treatment.

View Article: PubMed Central - PubMed

Affiliation: Genomic Medicine Institute, Learner Research Institute.

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Related in: MedlinePlus

Short-hairpin SRC reduced migration and induced apoptosis in FTC133-PTEN wild-type cells, but not in FTC236-PTEN ) cells. (A) Wound healing migration rates normalization in SRC-silenced FTC133-PTEN wild-type cells (left) and FTC236-PTEN ) cells (right). The results are the mean ± SE of three independent experiments with n = 5 in each condition. *P < 0.05. (B) TUNEL staining of apoptotic cells in SRC-silenced FTC133-PTEN wild-type cells with or without H2O2 exposure (left) and SRC-silenced FTC236-PTEN  cells with or without H2O2 exposure (right). Magnification: ×200. Experiments were performed five independent times. (C) Nuclear PTEN in SRC-silenced FTC133-PTEN wild-type cells and control FTC133-PTEN wild-type cells (transfected with empty vector) with or without H2O2, with or without bosutinib. Western blots were performed four independent times.
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DDU425F3: Short-hairpin SRC reduced migration and induced apoptosis in FTC133-PTEN wild-type cells, but not in FTC236-PTEN ) cells. (A) Wound healing migration rates normalization in SRC-silenced FTC133-PTEN wild-type cells (left) and FTC236-PTEN ) cells (right). The results are the mean ± SE of three independent experiments with n = 5 in each condition. *P < 0.05. (B) TUNEL staining of apoptotic cells in SRC-silenced FTC133-PTEN wild-type cells with or without H2O2 exposure (left) and SRC-silenced FTC236-PTEN cells with or without H2O2 exposure (right). Magnification: ×200. Experiments were performed five independent times. (C) Nuclear PTEN in SRC-silenced FTC133-PTEN wild-type cells and control FTC133-PTEN wild-type cells (transfected with empty vector) with or without H2O2, with or without bosutinib. Western blots were performed four independent times.

Mentions: SRC-silenced FTC133-PTEN wild-type cells showed decreased migration compared with shCon FTC133-PTEN wild-type cells. No significant difference was observed between SRC-silenced FTC236-PTEN cells and control FTC236-PTEN cells (transfected with empty vector) (Fig. 3A). Upon H2O2 treatment, more induced apoptosis was observed in SRC-silenced FTC133-PTEN wild-type compared with FTC133-PTEN wild-type control cells (with empty vector). No significant difference in apoptosis was observed between SRC-silenced FTC236-PTEN and FTC236-PTEN control cells (with empty vector) (Fig. 3B).Figure 3.


Cowden syndrome-associated germline SDHD variants alter PTEN nuclear translocation through SRC-induced PTEN oxidation.

Yu W, He X, Ni Y, Ngeow J, Eng C - Hum. Mol. Genet. (2014)

Short-hairpin SRC reduced migration and induced apoptosis in FTC133-PTEN wild-type cells, but not in FTC236-PTEN ) cells. (A) Wound healing migration rates normalization in SRC-silenced FTC133-PTEN wild-type cells (left) and FTC236-PTEN ) cells (right). The results are the mean ± SE of three independent experiments with n = 5 in each condition. *P < 0.05. (B) TUNEL staining of apoptotic cells in SRC-silenced FTC133-PTEN wild-type cells with or without H2O2 exposure (left) and SRC-silenced FTC236-PTEN  cells with or without H2O2 exposure (right). Magnification: ×200. Experiments were performed five independent times. (C) Nuclear PTEN in SRC-silenced FTC133-PTEN wild-type cells and control FTC133-PTEN wild-type cells (transfected with empty vector) with or without H2O2, with or without bosutinib. Western blots were performed four independent times.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4262496&req=5

DDU425F3: Short-hairpin SRC reduced migration and induced apoptosis in FTC133-PTEN wild-type cells, but not in FTC236-PTEN ) cells. (A) Wound healing migration rates normalization in SRC-silenced FTC133-PTEN wild-type cells (left) and FTC236-PTEN ) cells (right). The results are the mean ± SE of three independent experiments with n = 5 in each condition. *P < 0.05. (B) TUNEL staining of apoptotic cells in SRC-silenced FTC133-PTEN wild-type cells with or without H2O2 exposure (left) and SRC-silenced FTC236-PTEN cells with or without H2O2 exposure (right). Magnification: ×200. Experiments were performed five independent times. (C) Nuclear PTEN in SRC-silenced FTC133-PTEN wild-type cells and control FTC133-PTEN wild-type cells (transfected with empty vector) with or without H2O2, with or without bosutinib. Western blots were performed four independent times.
Mentions: SRC-silenced FTC133-PTEN wild-type cells showed decreased migration compared with shCon FTC133-PTEN wild-type cells. No significant difference was observed between SRC-silenced FTC236-PTEN cells and control FTC236-PTEN cells (transfected with empty vector) (Fig. 3A). Upon H2O2 treatment, more induced apoptosis was observed in SRC-silenced FTC133-PTEN wild-type compared with FTC133-PTEN wild-type control cells (with empty vector). No significant difference in apoptosis was observed between SRC-silenced FTC236-PTEN and FTC236-PTEN control cells (with empty vector) (Fig. 3B).Figure 3.

Bottom Line: However, very little is known about the underlying crosstalk between SDHD and PTEN in CS-associated thyroid cancer.We show that SRC inhibition could rescue SDHD dysfunction-induced cellular phenotype and tumorigenesis only when wild-type PTEN is expressed, in thyroid cancer lines.Patient lymphoblast cells carrying either SDHD-G12S or SDHD-H50R also show increased nuclear PTEN and more oxidized PTEN after hydrogen peroxide treatment.

View Article: PubMed Central - PubMed

Affiliation: Genomic Medicine Institute, Learner Research Institute.

Show MeSH
Related in: MedlinePlus