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N-(4-hydroxyphenyl)retinamide (4-HPR) modulates GADD45 expression in radiosensitive bladder cancer cell lines.

Publication ,  Journal Article
Zou, C; Guan, Y; Zou, C; Wang, J; Wang, L-E; Liebert, M; Grossman, HB; Wei, Q
Published in: Cancer Lett
June 28, 2002

We previously demonstrated that N-(4-hydroxyphenyl)retinamide (4-HPR) and gamma-irradiation, when used in combination, had a synergistic effect in inducing apoptosis in bladder cancer cells, suggesting that 4-HPR may increase radiosensitivity in bladder cancer cells. To unravel molecular correlates in this radiosensitizing effect of 4-HPR, we examined the baseline and 4-HPR-induced expression of GADD45 to elucidate possible mechanisms by which 4-HPR enhanced the effect of gamma-irradiation in three bladder cancer cell lines. To investigate the role of p53 in mediating the radiosensitizing effect of 4-HPR, we also examined mutations in exons 5-9 by using direct sequencing and the levels of p53 expression by using RT-PCR and Western blot, before and after treatment with 4-HPR in these bladder cancer cell lines. Two cell lines had low expression of GADD45, and a dose-dependent increase in GADD45 expression induced by 4-HPR was found in bladder cancer cell lines without p53 mutations in exons 5-9. A combination of gamma-irradiation and 4-HPR showed a significantly greater effect in enhancing GADD45 expression than either agent used alone. The results indicate that the combined treatment with 4-HPR and gamma-irradiation has a stronger effect on GADD45 expression than the treatment with either agent alone, which suggests that the two agents may have an additive/synergistic effect. However, a normal p53 function appears to be necessary for the dose-dependent induction of GADD45 by 4-HPR. Once our results are verified and replicated by other investigators, 4-HPR may have a potential clinical implication in effectively treating bladder cancer in combination with low-gamma-irradiation therapy.

Duke Scholars

Published In

Cancer Lett

DOI

ISSN

0304-3835

Publication Date

June 28, 2002

Volume

180

Issue

2

Start / End Page

131 / 137

Location

Ireland

Related Subject Headings

  • Urinary Bladder Neoplasms
  • Tumor Cells, Cultured
  • Radiation Tolerance
  • Proteins
  • Oncology & Carcinogenesis
  • Mutation
  • Intracellular Signaling Peptides and Proteins
  • Humans
  • Genes, p53
  • Gene Expression Regulation, Neoplastic
 

Citation

APA
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Zou, C., Guan, Y., Wang, J., Wang, L.-E., Liebert, M., Grossman, H. B., & Wei, Q. (2002). N-(4-hydroxyphenyl)retinamide (4-HPR) modulates GADD45 expression in radiosensitive bladder cancer cell lines. Cancer Lett, 180(2), 131–137. https://doi.org/10.1016/s0304-3835(01)00864-3
Zou, Changping, Yongli Guan, Changchun Zou, Jian Wang, Li-E Wang, Monica Liebert, H Barton Grossman, and Qingyi Wei. “N-(4-hydroxyphenyl)retinamide (4-HPR) modulates GADD45 expression in radiosensitive bladder cancer cell lines.Cancer Lett 180, no. 2 (June 28, 2002): 131–37. https://doi.org/10.1016/s0304-3835(01)00864-3.
Zou C, Guan Y, Wang J, Wang L-E, Liebert M, Grossman HB, et al. N-(4-hydroxyphenyl)retinamide (4-HPR) modulates GADD45 expression in radiosensitive bladder cancer cell lines. Cancer Lett. 2002 Jun 28;180(2):131–7.
Zou, Changping, et al. “N-(4-hydroxyphenyl)retinamide (4-HPR) modulates GADD45 expression in radiosensitive bladder cancer cell lines.Cancer Lett, vol. 180, no. 2, June 2002, pp. 131–37. Pubmed, doi:10.1016/s0304-3835(01)00864-3.
Zou C, Guan Y, Wang J, Wang L-E, Liebert M, Grossman HB, Wei Q. N-(4-hydroxyphenyl)retinamide (4-HPR) modulates GADD45 expression in radiosensitive bladder cancer cell lines. Cancer Lett. 2002 Jun 28;180(2):131–137.
Journal cover image

Published In

Cancer Lett

DOI

ISSN

0304-3835

Publication Date

June 28, 2002

Volume

180

Issue

2

Start / End Page

131 / 137

Location

Ireland

Related Subject Headings

  • Urinary Bladder Neoplasms
  • Tumor Cells, Cultured
  • Radiation Tolerance
  • Proteins
  • Oncology & Carcinogenesis
  • Mutation
  • Intracellular Signaling Peptides and Proteins
  • Humans
  • Genes, p53
  • Gene Expression Regulation, Neoplastic