Majority of TP53 signaling pathway related genes are up-regulated in Tamoxifen-treated MCF-7 human Breast adenocarcinoma cell line

  • سال انتشار: 1396
  • محل انتشار: دومین کنگره بین المللی پزشکی شخصی
  • کد COI اختصاصی: IPMCMED02_036
  • زبان مقاله: انگلیسی
  • تعداد مشاهده: 397
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نویسندگان

Milad Rouhimoghadam

Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran

Shahrokh Safarian

Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran

چکیده

Worldwide, breast cancer is the most common cancer in women, with an estimated 1.38 million new cases diagnosed per year. Tamoxifen has been widely used to treat breast cancer as an endocrine therapy. Apoptosis, or programmed cell death, is critical for embryogenesis and for normal tissue homeostasis. The ability of p53 to control passage through the cell cycle (in G1 and in G2) and to control apoptosis in response to abnormal proliferative signals and stress including DNA damage is considered to be important for its tumor suppression function. The ability of tamoxifen to inhibit proliferation has been extensively studied. However, the molecular mechanism by which tamoxifen initiates apoptosis is poorly understood.Methods:MCF-7 cells were treated with 250µM Tamoxifen for 48 hours and cultivated at 37 °C in a 5% (vol/vol) CO2 environment. RNA was extracted and samples were prepared according to standardized protocols before being sequenced on an Illumina HiSeq 4000 sequencing system. We apply Cuffdiff 2, an algorithm that estimates expression at transcript-level resolution and controls for variability evident across replicate libraries.Results:Our data from differential expression studies and pathway enrichment analysis display that in Tamoxifen-treated sample group (in comparison to control group) 19 genes related to p53 signaling axis (CDKN1A; GADD45B; GADD45A; GORAB; TNFRSF10B; RCHY1; PPM1D; GADD45G; CASP8; ZMAT3; CASP3; SESN1; SESN2; FAS; CYCS; PMAIP1; MDM4; SFN; TP53) are over-expressed by the adjusted p.value of 0.00715.Discussion:In addition to its role in suppressing tumorigenesis, p53-dependent apoptosis contributes to chemotherapy-induced cell death. These findings indicated that Tamoxifen as a potent chemopreventive drug can effectively trigger apoptotic cell death through activation of TP53 signaling axis.

کلیدواژه ها

TP53, Breast cancer, Tamoxifen, Apoptosis

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