TROP2 methylation and expression in tamoxifen-resistant breast cancer

Cancer Cell International
Stephanie M ZimmersKathleen F Arcaro

Abstract

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. 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. 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 m...Continue Reading

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Citations

Aug 10, 2020·Indian Journal of Pathology & Microbiology·Serkan Y Celik, Özgür İlhan Çelik
Nov 15, 2020·Cancers·Sára LenártPetr Beneš
Feb 23, 2021·Oral Diseases·Mauricio Rocha DouradoRicardo D Coletta

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Methods Mentioned

BETA
PCR
Assay
transfection

Software Mentioned

Pyromark Assay Design
Illumina Genome Studio Methylation Module
Genome Studio
Primer
StatPlus
Pyromark Q24
BLAST
Excel
Genome Studio Methylation Module

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