Open Access

Altered histone acetylation patterns in pancreatic cancer cell lines induce subtype‑specific transcriptomic and phenotypical changes

  • Authors:
    • Quan Zhou
    • Svenja Pichlmeier
    • Anna Maria Denz
    • Nicole Schreiner
    • Tobias Straub
    • Simone Benitz
    • Julia Wolff
    • Lisa Fahr
    • Maria Del Socorro Escobar Lopez
    • Jörg Kleeff
    • Julia Mayerle
    • Ujjwal Mukund Mahajan
    • Ivonne Regel
  • View Affiliations

  • Published online on: January 16, 2024     https://doi.org/10.3892/ijo.2024.5614
  • Article Number: 26
  • Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at advanced tumor stages with chemotherapy as the only treatment option. Transcriptomic analysis has defined a classical and basal‑like PDAC subtype, which are regulated by epigenetic modification. The present study aimed to determine if drug‑induced epigenetic reprogramming of pancreatic cancer cells affects PDAC subtype identity and chemosensitivity. Classical and basal‑like PDAC cell lines PaTu‑S, Capan‑1, Capan‑2, Colo357, PaTu‑T, PANC‑1 and MIAPaCa‑2, were treated for a short (up to 96 h) and long (up to 30 weeks) period with histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors. The cells were analyzed using gene expression approaches, immunoblot analysis, and various cell assays to assess cell characteristics, such as proliferation, colony formation, cell migration and sensitivity to chemotherapeutic drugs. Classical and basal‑like PDAC cell lines showed pronounced epigenetic regulation of subtype‑specific genes through acetylation of lysine 27 on Histone H3 (H3K27ac). Moreover, classical cell lines revealed a significantly decreased expression of HDAC2 and increased total levels of H3K27ac in comparison with the basal‑like cell lines. Following HAT inhibitor treatment, classical cell lines exhibited a loss of epithelial marker gene expression, decreased chemotherapy response gene score and increased cell migration in vitro, indicating a tumor‑promoting phenotype. HDAC inhibitor treatment, however, exerted minimal reprogramming effects in both subtypes. Epigenetic reprogramming of classical and basal‑like tumor cells did not have a major impact on gemcitabine response, although the gemcitabine transporter gene SLC29A1 (solute carrier family 29 member 1) was epigenetically regulated.
View References

Related Articles

Journal Cover

March-2024
Volume 64 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
Zhou Q, Pichlmeier S, Denz AM, Schreiner N, Straub T, Benitz S, Wolff J, Fahr L, Del Socorro Escobar Lopez M, Kleeff J, Kleeff J, et al: Altered histone acetylation patterns in pancreatic cancer cell lines induce subtype‑specific transcriptomic and phenotypical changes. Int J Oncol 64: 26, 2024.
APA
Zhou, Q., Pichlmeier, S., Denz, A.M., Schreiner, N., Straub, T., Benitz, S. ... Regel, I. (2024). Altered histone acetylation patterns in pancreatic cancer cell lines induce subtype‑specific transcriptomic and phenotypical changes. International Journal of Oncology, 64, 26. https://doi.org/10.3892/ijo.2024.5614
MLA
Zhou, Q., Pichlmeier, S., Denz, A. M., Schreiner, N., Straub, T., Benitz, S., Wolff, J., Fahr, L., Del Socorro Escobar Lopez, M., Kleeff, J., Mayerle, J., Mahajan, U. M., Regel, I."Altered histone acetylation patterns in pancreatic cancer cell lines induce subtype‑specific transcriptomic and phenotypical changes". International Journal of Oncology 64.3 (2024): 26.
Chicago
Zhou, Q., Pichlmeier, S., Denz, A. M., Schreiner, N., Straub, T., Benitz, S., Wolff, J., Fahr, L., Del Socorro Escobar Lopez, M., Kleeff, J., Mayerle, J., Mahajan, U. M., Regel, I."Altered histone acetylation patterns in pancreatic cancer cell lines induce subtype‑specific transcriptomic and phenotypical changes". International Journal of Oncology 64, no. 3 (2024): 26. https://doi.org/10.3892/ijo.2024.5614