Kdm6a and Kdm6b: Altered expression in malignant pleural mesothelioma

  • Authors:
    • Sian Cregan
    • Maeve Breslin
    • Gerard Roche
    • Sigrid Wennstedt
    • Lauren MacDonagh
    • Cinaria Albadri
    • Yun Gao
    • Kenneth J. O'Byrne
    • Sinead Cuffe
    • Stephen P. Finn
    • Steven G. Gray
  • View Affiliations

  • Published online on: February 9, 2017     https://doi.org/10.3892/ijo.2017.3870
  • Pages: 1044-1052
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Malignant pleural mesothelioma (MPM) is a rare aggressive cancer of the pleura primarily associated with prior exposure to asbestos. The current standard of care for patients suffering from MPM is a combination of cisplatin and pemetrexed (or alternatively cisplatin and raltitrexed). Most patients, however, die within 24 months of diagnosis. New therapies are therefore urgently required for this disease. Inflammation is thought to be a key element in the pathogenesis of MPM, and recently Kdm6 family members (Kdm6a and Kdm6b) have been identified as playing important roles in inflammatory processes. As such these genes could potentially represent novel candidate targets for intervention in MPM. Using RT-PCR we examined the expression of Kdm6aA and Kdm6b in a panel of MPM cell lines and in a cohort of snap-frozen patient samples isolated at surgery comprising benign, epithelial, biphasic and sarcomatoid histologies. Both Kdm6a and Kdm6b were found to be significantly overexpressed in MPM at the mRNA level. However, tests examining if targeting therapeutically Kdm6a/b using a specific small molecule inhibitor (GSK-J4) was potentially useful for treating MPM, revealed that anti-proliferative activity was higher at lower drug concentrations in cell lines derived from normal mesothelial cells compared to those derived from malignant cells. Treatments with GSK-J4 were found to be associated with the induction of apoptosis and increased expression of pro-inflammatory cytokines. As such our results demonstrate that whilst members of the Kdm6 family are overexpressed in MPM they may not be suitable candidates for therapy and may elicit a cytokine storm.
View Figures
View References

Related Articles

Journal Cover

March-2017
Volume 50 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Cregan S, Breslin M, Roche G, Wennstedt S, MacDonagh L, Albadri C, Gao Y, O'Byrne KJ, Cuffe S, Finn SP, Finn SP, et al: Kdm6a and Kdm6b: Altered expression in malignant pleural mesothelioma. Int J Oncol 50: 1044-1052, 2017
APA
Cregan, S., Breslin, M., Roche, G., Wennstedt, S., MacDonagh, L., Albadri, C. ... Gray, S.G. (2017). Kdm6a and Kdm6b: Altered expression in malignant pleural mesothelioma. International Journal of Oncology, 50, 1044-1052. https://doi.org/10.3892/ijo.2017.3870
MLA
Cregan, S., Breslin, M., Roche, G., Wennstedt, S., MacDonagh, L., Albadri, C., Gao, Y., O'Byrne, K. J., Cuffe, S., Finn, S. P., Gray, S. G."Kdm6a and Kdm6b: Altered expression in malignant pleural mesothelioma". International Journal of Oncology 50.3 (2017): 1044-1052.
Chicago
Cregan, S., Breslin, M., Roche, G., Wennstedt, S., MacDonagh, L., Albadri, C., Gao, Y., O'Byrne, K. J., Cuffe, S., Finn, S. P., Gray, S. G."Kdm6a and Kdm6b: Altered expression in malignant pleural mesothelioma". International Journal of Oncology 50, no. 3 (2017): 1044-1052. https://doi.org/10.3892/ijo.2017.3870