TROP2 methylation and expression in tamoxifen-resistant breast cancer.

Autor: Zimmers SM; 1Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, Life Sciences Laboratories, Room 540D, 240 Thatcher Road, Amherst, MA 01003 USA., Browne EP; 1Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, Life Sciences Laboratories, Room 540D, 240 Thatcher Road, Amherst, MA 01003 USA., Williams KE; 1Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, Life Sciences Laboratories, Room 540D, 240 Thatcher Road, Amherst, MA 01003 USA., Jawale RM; 2Pathology Department, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199 USA., Otis CN; 2Pathology Department, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199 USA., Schneider SS; 1Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, Life Sciences Laboratories, Room 540D, 240 Thatcher Road, Amherst, MA 01003 USA.; 3Biospecimen Resource and Molecular Analysis Facility, Baystate Medical Center, 3601 Main Street, Springfield, MA 01199 USA., Arcaro KF; 1Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, Life Sciences Laboratories, Room 540D, 240 Thatcher Road, Amherst, MA 01003 USA.
Jazyk: angličtina
Zdroj: Cancer cell international [Cancer Cell Int] 2018 Jul 06; Vol. 18, pp. 94. Date of Electronic Publication: 2018 Jul 06 (Print Publication: 2018).
DOI: 10.1186/s12935-018-0589-9
Abstrakt: Background: The DNA methyltransferase 1 inhibitor, 5-Aza-2'-deoxycytidine (5-Aza-dC) is a potential treatment for breast cancer. However, not all breast tumors will respond similarly to treatment with 5-Aza-dC, and little is known regarding the response of hormone-resistant breast cancers to 5-Aza-dC.
Methods: We demonstrate that 5-Aza-dC-treatment has a stronger effect on an estrogen receptor-negative, Tamoxifen-selected cell line, TMX2-28, than on the estrogen receptor-positive, MCF7, parental cell line. Using data obtained from the HM450 Methylation Bead Chip, pyrosequencing, and RT-qPCR, we identified a panel of genes that are silenced by promoter methylation in TMX2-28 and re-expressed after treatment with 5-Aza-dC.
Results: One of the genes identified, tumor associated calcium signal transducer 2 ( TACSTD2 ), is altered by DNA methylation, and there is evidence that in some cancers decreased expression may result in greater proliferation. Analysis of DNA methylation of TACSTD2 and protein expression of its product, trophoblast antigen protein 2 (TROP2), was extended to a panel of primary (n = 34) and recurrent (n = 34) breast tumors. Stratifying tumors by both recurrence and ER status showed no significant relationship between TROP2 levels and TACSTD2 methylation. Knocking down TACSTD2 expression in MCF7 increased proliferation however; re-expressing TACSTD2 in TMX2-28 did not inhibit proliferation, indicating that TACSTD2 re-expression alone was insufficient to explain the decreased proliferation observed after treatment with 5-Aza-dC.
Conclusions: These results illustrate the complexity of the TROP2 signaling network. However, TROP2 may be a valid therapeutic target for some cancers. Further studies are needed to identify biomarkers that indicate how TROP2 signaling affects tumor growth and whether targeting TROP2 would be beneficial to the patient.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje