Aldehyde dehydrogenase 3A1 promotes multi-modality resistance and alters gene expression profile in human breast adenocarcinoma MCF-7 cells

Georgia Persephoni Voulgaridou, Magdalini Kiziridou, Theodora Mantso, Katerina Chlichlia, Alex Galanis, Michael I. Koukourakis, Rodrigo Franco-Cruz, Mihalis I. Panayiotidis, Aglaia Pappa

Research output: Contribution to journalArticle

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Abstract

Aldehyde dehydrogenases participate in a variety of cellular homeostatic mechanisms like metabolism, proliferation, differentiation, apoptosis, whereas recently, they have been implicated in normal and cancer cell stemness. We explored roles for ALDH3A1 in conferring resistance to chemotherapeutics/radiation/oxidative stress and whether ectopic overexpression of ALDH3A1 could lead to alterations of gene expression profile associated with cancer stem cell-like phenotype. MCF-7 cells were stably transfected either with an empty vector (mock) or human aldehyde dehydrogenase 3A1 cDNA. The expression of aldehyde dehydrogenase 3A1 in MCF-7 cells was associated with altered cell proliferation rate and enhanced cell resistance against various chemotherapeutic drugs (4-hydroxyperoxycyclophosphamide, doxorubicin, etoposide, and 5-fluorouracil). Aldehyde dehydrogenase 3A1 expression also led to increased tolerance of MCF-7 cells to gamma radiation and hydrogen peroxide-induced stress. Furthermore, aldehyde dehydrogenase 3A1-expressing MCF-7 cells exhibited gene up-regulation of cyclins A, B1, B2, and down-regulation of cyclin D1 as well as transcription factors p21, CXR4, Notch1, SOX2, SOX4, OCT4, and JAG1. When compared to mock cells, no changes were observed in mRNA levels of ABCA2 and ABCB1 protein pumps with only a minor decrease of the ABCG2 pump in the aldehyde dehydrogenase 3A1-expressing cells. Also, the adhesion molecules EpCAM and CD49F were also found to be up-regulated in aldehyde dehydrogenase 3A1expressing cells. Taken together, ALDH3A1 confers a multi-modality resistance phenotype in MCF-7 cells associated with slower growth rate, increased clonogenic capacity, and altered gene expression profile, underlining its significance in cell homeostasis.

Original languageEnglish (US)
Pages (from-to)120-128
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume77
DOIs
StatePublished - Aug 1 2016

Fingerprint

Aldehyde Dehydrogenase
MCF-7 Cells
Transcriptome
Gene expression
Adenocarcinoma
Breast
Pumps
Cyclin B1
Phenotype
Cyclin A
Oxidative stress
Neoplastic Stem Cells
Cyclin D1
Gamma Rays
Cell proliferation
P-Glycoprotein
Etoposide
Stem cells
Metabolism
Fluorouracil

Keywords

  • ALDH
  • ALDH3A1
  • Breast cancer
  • CD49F
  • Cancer stem cells
  • Chemoresistance
  • EpCAM
  • MCF-7
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Aldehyde dehydrogenase 3A1 promotes multi-modality resistance and alters gene expression profile in human breast adenocarcinoma MCF-7 cells. / Voulgaridou, Georgia Persephoni; Kiziridou, Magdalini; Mantso, Theodora; Chlichlia, Katerina; Galanis, Alex; Koukourakis, Michael I.; Franco-Cruz, Rodrigo; Panayiotidis, Mihalis I.; Pappa, Aglaia.

In: International Journal of Biochemistry and Cell Biology, Vol. 77, 01.08.2016, p. 120-128.

Research output: Contribution to journalArticle

Voulgaridou, Georgia Persephoni ; Kiziridou, Magdalini ; Mantso, Theodora ; Chlichlia, Katerina ; Galanis, Alex ; Koukourakis, Michael I. ; Franco-Cruz, Rodrigo ; Panayiotidis, Mihalis I. ; Pappa, Aglaia. / Aldehyde dehydrogenase 3A1 promotes multi-modality resistance and alters gene expression profile in human breast adenocarcinoma MCF-7 cells. In: International Journal of Biochemistry and Cell Biology. 2016 ; Vol. 77. pp. 120-128.
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AU - Mantso, Theodora

AU - Chlichlia, Katerina

AU - Galanis, Alex

AU - Koukourakis, Michael I.

AU - Franco-Cruz, Rodrigo

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AU - Pappa, Aglaia

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