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Triiodothyronine regulates indirectly Amphiregulin gene expression in estrogen‐positive breast cancer cell line. (LB494)
Author(s) -
Conde Sandro,
De Síbio Maria,
De Oliveira Miriane,
Moretto Fernanda,
Olímpio Regiane,
Luvizon Aline,
Padovani Carlos,
Nogueira Celia
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb494
Subject(s) - amphiregulin , fulvestrant , gene expression , estrogen receptor , oncogene , biology , regulation of gene expression , endocrinology , medicine , cancer research , breast cancer , cancer , receptor , gene , cell cycle , epidermal growth factor , genetics
Amphiregulin (AREG) is considered an oncogene whose expression is related to several types of cancer. Our group identified a triiodothyronine (T3) action on different genes of breast cancer cell lines through the microarray approach, including AREG; however, there are no works about how T3 regulates AREG gene expression. The relation between AREG and T3 remains unclear and, for this reason, in this study we are looking for nuclear and extra‐nuclear action of T3 on AREG gene expression in MCF‐7, an estrogen‐receptor‐positive breast cancer cell line. Cells were treated with 10‐8 M T3 for 10, 30, 60 and 240 minutes, separately. Treatments were organized with or without Cycloheximide (CHX ‐ 50uM), a protein synthesis inhibitor, and with or without Fulvestrant (ICI ‐ 1uM), an estrogen receptor antagonist. The mRNA was analyzed by real‐time PCR approach. T3 increases gene expression of AREG in MCF‐7 cell lines, independently of incubation time, but this action was converted to the control level when T3 was associated with CHX, indicating that prior protein synthesis is required in this process. Addition of ICI to T3 for 10 minutes augmented gene expression in relation to those cells treated only with T3, but after 30 minutes, ICI plus T3 decreased AREG gene expression when compared with T3 itself. Therefore, T3 regulation of AREG gene expression is dependent on prior protein synthesis and estrogen receptor. Estrogen receptor is necessary for AREG gene expression in contrary ways when comparing 10 minutes with 30, 60, 240 minutes. The alteration in AREG gene expression is dependent on the time elapsed after the treatment, indicating that metabolism changes could be altered after 10 minutes in T3‐dependent AREG gene expression. Grant Funding Source : Supported by FAPESP grant 2009/15607‐2 and 2013/‐8