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The determination of changes in the expression of genes for selected specific transcriptional factors in in vitro ductal breast cancer cells under the influence of paclitaxel

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Abstract

This study aimed to determine the changes in the expression of genes for selected specific transcriptional factors that have both activating and repressing functions in in vitro ductal breast cancer cells, under the influence of paclitaxel, applying the microarray technique. The cells are treated with 60 ng/ml and 300 ng/ml doses of paclitaxel that correspond to those applied in breast cancer therapy. About 60 ng/ml doses of paclitaxel cause a statistically significant increase in expression of all the 16 analysed genes coding transcriptional factors, ranging from 1.84-fold (for PO4F2) to 4.65-fold (for LMO4) (p < 0.05) in comparison with the control cells, and enhanced the taxane mechanism of action. The 300 ng/ml doses of paclitaxel cause a cytotoxic effect in the cells. In this article, we argue that these changes in gene expression values may constitute prognostic and predictive factors in ductal breast cancer therapy.

Abbreviations

Bak:

BCL2-antagonist/killer

Bax:

BCL2-associated X protein

Bcl-2:

B-cell CLL/lymphoma 2

BRCA1:

breast cancer type 1 susceptibility protein

cDNA:

complementary deoxyribonucleic acid

CTCF :

CCCTC-binding factor (zinc finger protein)

CtIP:

retinoblastoma binding protein 8

DCIS:

ductal carcinoma in situ

DMSO:

dimethyl sulfoxide

dNTPs:

deoxynucleotide triphosphates

FBS:

fetal bovine serum

GSTP1 :

glutathione S-transferase pi 1

HOXA1 :

homeo box A1

HOXA5 :

homeo box A5

HSP-27:

heat shock 27kDa protein 1

KLF4 :

Kruppel-like factor 4 (gut) Kruppel

LMO4 :

LIM domain only 4

MADH4 :

SMAD family member 4

MAPs:

microtubule-associated proteins

MBD2 :

methyl-CpG binding domain protein

MCF10A:

human mammary epithelial cell line

MCF-7:

human breast adenocarcinoma cell line

Myb:

v-myb myeloblastosis viral oncogene homolog (avian)

Myc:

v-myc myelocytomatosis viral oncogene homolog (avian)

p53:

tumour protein p53

PDEF :

SAM pointed domain containing ets transcription factor

PHB :

prohibitin

POU4F2 :

POU domain, class 4, transcription factor 2

PTX:

paclitaxel

Rb:

retinoblastoma 1

RNA:

ribonucleic acid

RPMI:

Roswell Park Memorial Institute medium

RUNX :

runt-related transcription factor 2

SMAD4:

SMAD4 SMAD, mothers against DPP homolog 4 (Drosophila)

TFAP2A :

transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha)

TFAP2C :

transcription factor AP-2 gamma (activating enhancer binding protein 2 gamma

TFs:

transcription factors

TGFα:

transforming growth factor alpha

TP63 :

P63 tumour protein p63

TP73 :

TP73L tumour protein p73-like

WT1:

Wilms’ tumour gene product

YY1 :

YY1 transcription factor

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Correspondence to Marta Ziaja-Sołtys.

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Key words

  • Breast cancer
  • Transcriptional factors
  • Gene expression
  • Microarrays
  • Anti-tumour
  • Treatment
  • Paclitaxel
  • Microtubules
  • Cytotoxic effect
  • Apoptosis