Limits...
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.

Show MeSH

Related in: MedlinePlus

Accumulation of oxidized nuclear PTEN from SDHD-G12S and SDHD-H50R was abolished with bosutinib pretreatment in 8505C cells. (A) Nuclear PTEN was measured in 8505C cells transfected with SDHD-wild type, -G12S and -H50R, respectively, after H2O2 exposure with or without bosutinib pretreatment. (B) Wound healing migration rates normalization in papillary thyroid carcinoma (PTC) cell line 8505C cells transfected with SDHD-WT, -G12S, or -H50R, respectively, with/without Bosutinib treatment (left) and 8505C cells co-transfected with shPTEN and SDHD-WT, -G12S or H50R, respectively, with/without Bosutinib treatment (right). The results are the mean ± SE of four independent experiments with n = 5 in each condition. *P < 0.05, ns: not significant (P > 0.05).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4262496&req=5

DDU425F5: Accumulation of oxidized nuclear PTEN from SDHD-G12S and SDHD-H50R was abolished with bosutinib pretreatment in 8505C cells. (A) Nuclear PTEN was measured in 8505C cells transfected with SDHD-wild type, -G12S and -H50R, respectively, after H2O2 exposure with or without bosutinib pretreatment. (B) Wound healing migration rates normalization in papillary thyroid carcinoma (PTC) cell line 8505C cells transfected with SDHD-WT, -G12S, or -H50R, respectively, with/without Bosutinib treatment (left) and 8505C cells co-transfected with shPTEN and SDHD-WT, -G12S or H50R, respectively, with/without Bosutinib treatment (right). The results are the mean ± SE of four independent experiments with n = 5 in each condition. *P < 0.05, ns: not significant (P > 0.05).

Mentions: To further determine if SDHDv affects PTEN function in papillary thyroid cancer cell line, we next transfected 8505C cells with SDHD wild-type, SDHD-G12S and SDHD-H50R plasmids, respectively. More nuclear PTEN was detected in 8505C cells transfected with SDHD-G12S and SDHD-H50R with H2O2 treatment. Consistent with FTC cell results, bosutinib pretreatment dramatically decreased nuclear PTEN accumulation (Fig. 5A). Wound healing migration assay showed increased migration in 8505C cells transfected with SDHD-G12S or SDHD-H50R, which were inhibited with SRC inhibition (Fig. 5B, left). When we knock down PTEN with shPTEN, SRC inhibitor bosutinib had no effect on migration in 8505C cells (Fig. 5B, right).Figure 5.


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)

Accumulation of oxidized nuclear PTEN from SDHD-G12S and SDHD-H50R was abolished with bosutinib pretreatment in 8505C cells. (A) Nuclear PTEN was measured in 8505C cells transfected with SDHD-wild type, -G12S and -H50R, respectively, after H2O2 exposure with or without bosutinib pretreatment. (B) Wound healing migration rates normalization in papillary thyroid carcinoma (PTC) cell line 8505C cells transfected with SDHD-WT, -G12S, or -H50R, respectively, with/without Bosutinib treatment (left) and 8505C cells co-transfected with shPTEN and SDHD-WT, -G12S or H50R, respectively, with/without Bosutinib treatment (right). The results are the mean ± SE of four independent experiments with n = 5 in each condition. *P < 0.05, ns: not significant (P > 0.05).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262496&req=5

DDU425F5: Accumulation of oxidized nuclear PTEN from SDHD-G12S and SDHD-H50R was abolished with bosutinib pretreatment in 8505C cells. (A) Nuclear PTEN was measured in 8505C cells transfected with SDHD-wild type, -G12S and -H50R, respectively, after H2O2 exposure with or without bosutinib pretreatment. (B) Wound healing migration rates normalization in papillary thyroid carcinoma (PTC) cell line 8505C cells transfected with SDHD-WT, -G12S, or -H50R, respectively, with/without Bosutinib treatment (left) and 8505C cells co-transfected with shPTEN and SDHD-WT, -G12S or H50R, respectively, with/without Bosutinib treatment (right). The results are the mean ± SE of four independent experiments with n = 5 in each condition. *P < 0.05, ns: not significant (P > 0.05).
Mentions: To further determine if SDHDv affects PTEN function in papillary thyroid cancer cell line, we next transfected 8505C cells with SDHD wild-type, SDHD-G12S and SDHD-H50R plasmids, respectively. More nuclear PTEN was detected in 8505C cells transfected with SDHD-G12S and SDHD-H50R with H2O2 treatment. Consistent with FTC cell results, bosutinib pretreatment dramatically decreased nuclear PTEN accumulation (Fig. 5A). Wound healing migration assay showed increased migration in 8505C cells transfected with SDHD-G12S or SDHD-H50R, which were inhibited with SRC inhibition (Fig. 5B, left). When we knock down PTEN with shPTEN, SRC inhibitor bosutinib had no effect on migration in 8505C cells (Fig. 5B, right).Figure 5.

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