Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation

Rosser, Charles J.; Tanaka, Motoyoshi; Pisters, Louis L.; Tanaka, Norifumi; Levy, Lawrence B.; Hoover, David C; Grossman, H. Barton; McDonnell, Timothy J.; Kuban, Deborah A.; Meyn, Raymond E.

doi:10.1038/sj.cgt.7700673

Cited by 58 publications

(41 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…48,49 This recovery of radiation sensitivity was attributed to the ability of PTEN to suppress DNA repair capacity. 50 In contrast, Shen and coworkers reported that PTEN is important for DNA DSB repair by regulating Rad51 expression 4 and that PTEN influences γ-H2AX as well as 53BP1 of spindle assembly checkpoint, a well characterized pathway to genomic instability.…”

Section: Discussionmentioning

confidence: 99%

Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair

Gupta¹,

Yang²,

Pandita³

et al. 2009

Cell Cycle

112

113

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair

Gupta¹,

Yang²,

Pandita³

et al. 2009

Cell Cycle

112

113

View full text Add to dashboard Cite

“…Loss of functional PTEN and the subsequent activation of the PI3K/Akt pathway may render cells more resistant to radiation treatment in advanced prostate cancer. Rosser et al (50) showed that adenoviral-mediated PTEN transgene expression sensitizes prostate cancer cells to radiation. Our study confirms the results from the earlier study and extend to show that the presence of PTEN enhances the radiosensitization effect of parthenolide, in part, by suppressing the absolute amount of activated p-Akt.…”

Section: Discussionmentioning

confidence: 99%

The radiosensitization effect of parthenolide in prostate cancer cells is mediated by nuclear factor-κB inhibition and enhanced by the presence of PTEN

Sun¹,

Clair²,

Fang³

et al. 2007

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Parthenolide has been shown to have anti-inflammatory and antitumor properties. However, whether and how parthenolide enhances tumor sensitivity to radiation therapy are unknown. In this study, we show that inhibition of the nuclear factor-KB (NF-KB) pathway is a common mechanism for the radiosensitization effect of parthenolide in prostate cancer cells LNCaP, DU145, and PC3. Parthenolide inhibits radiation-induced NF-KB DNAbinding activity and the expression of its downstream target sod2, the gene coding for an important antiapoptotic and antioxidant enzyme (manganese superoxide dismutase) in the three prostate cancer cells. Different susceptibilities to parthenolide's effect are observed in two radioresistant cancer cells, DU145 and PC3, with DU145 cells showing higher sensitivity. This differential susceptibility to parthenolide is due, in part, to the fact that in addition to NF-KB inhibition, parthenolide activates the phosphatidylinositol-3-kinase/Akt prosurvival pathway in both cell lines. However, the activated Akt in DU145 cells is kept at a relatively low level compared with that in PC3 cells due to the presence of functional PTEN. Transfection of wild-type PTEN into PTEN-null cells, PC3, confers the enhanced radiosensitization effect of parthenolide in PTEN-expressing cells. When PTEN expression is knocked down in DU145 cells, the cells become more resistant to parthenolide's effect. Taken together, these results suggest that parthenolide inhibits the NF-KB pathway and activates the phosphatidylinositol-3-kinase/Akt pathway in prostate cancer cells. The radiosensitization effect of parthenolide is due, in part, to the inhibition of the NF-KB pathway. The presence of PTEN enhances the radiosensitization effect of parthenolide, in part, by suppressing the absolute amount of activated p-Akt. [Mol Cancer Ther 2007;6(9):2477 -86]

show abstract

“…Prior reports have indicated that restoring PTEN function in PTEN-defective cells using gene transfer approaches radiosensitizes human glioma 19 and prostate carcinoma 20 cells. The molecular mechanism responsible for the radiosensitizing properties of Ad-PTEN has not been known, and the ability of Ad-PTEN to retard the repair of radiation-induced DSBs, shown here, has not been demonstrated before.…”

Section: Adenoviral Pten Enhances Radiosensitivity G Pappas Et Almentioning

confidence: 99%

“…20 Mutations in PTEN are relatively frequent in prostate cancer, but its status in NSCLC has been studied less often. One study found that abnormalities of the PTEN gene were involved in only a small subset of lung cancers.…”

Section: Introductionmentioning

confidence: 99%

Adenoviral-mediated PTEN expression radiosensitizes non-small cell lung cancer cells by suppressing DNA repair capacity

et al. 2007

View full text Add to dashboard Cite

Expression of the PTEN tumor suppressor gene is abnormal in many human cancers. Loss of PTEN expression leads to the activation of downstream signaling pathways that have been associated with resistance to radiation. In non-small cell lung carcinoma (NSCLC), suppressed expression of PTEN is frequently due to methylation of its promoter region. In this study, we tested whether gene transfer of wild-type PTEN into an NSCLC cell line with a known methylated PTEN promoter, H1299, would increase its sensitivity to ionizing radiation. Pretreating H1299 cells with an adenoviral-mediated PTEN (Ad-PTEN)-expressing vector sensitized H1299 cells to radiation. To determine the mechanism responsible for radiosensitization, we first examined radiation-induced apoptosis, which was enhanced but did not correlate with radiosensitizing effect of Ad-PTEN. Therefore, we next examined the ability of Ad-PTEN to modulate the repair of radiation-induced DNA double-strand breaks (DSBs) using the detection of repair foci positive for g-H2AX, a protein that becomes evident at the sites of each DSB and that can be visualized by immunofluorescent staining. Compared with controls, the repair of radiation-induced DSBs was retarded in H1299 cells pretreated with Ad-PTEN, consistent with the radiosensitizing effect of the vector. We conclude that signal transduction pathways residing primarily in the cytoplasm may intersect with DNA damage and repair pathways in the nucleus to modulate cellular responses to radiation. Elucidating the mechanisms responsible for this intersection may lead to novel strategies for improving therapy for cancers with defective PTEN.

show abstract

Adenoviral-mediated PTEN transgene expression sensitizes Bcl-2-expressing prostate cancer cells to radiation

Cited by 58 publications

References 16 publications

Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair

Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair

The radiosensitization effect of parthenolide in prostate cancer cells is mediated by nuclear factor-κB inhibition and enhanced by the presence of PTEN

Adenoviral-mediated PTEN expression radiosensitizes non-small cell lung cancer cells by suppressing DNA repair capacity

Contact Info

Product

Resources

About