Genes related to growth regulation, DNA repair and apoptosis in an oestrogen receptor-negative (MDA-231) versus an oestrogen receptor-positive (MCF-7) breast tumour cell line.
The molecular mechanism(s) behind the development of endocrine resistance in breast cancer remains controversial. Here, we compare the capability of oestrogen receptor (ER)-negative cells (MDA-231) versus ER-positive tamoxifen-sensitive cells (MCF-7) to handle DNA repair, transmit signals from damaged DNA, initiate cell death via apoptosis, and then to control transmitted signals from the cell cycle and to synthesize growth factors and receptors. Genes related to these events were studied by cDNA micro-array. Normal human breast cells (H2F) and human lymphoblastoid tumour cells (CEM) were used as controls. Of the 18 genes investigated, 10 genes showed differences in their expression between the cell types. The ER-negative cells showed higher expressions of BRCA1, BRCA2, cdc2, cyclin B1, cyclin D1, cyclin E, IGFBP-3, TGF-alpha, TGF beta 2 and a lower expression of TGF beta R1. No differences in the expressions of bax, bcl-2, p53, p21 and GADD45 were found between the two cell lines. We found that the ER-negative cells were characterized by: (1) a stimulated expression of growth factors and cell cycle regulation compounds, (2) improved DNA repair capacity, but (3) no change in DNA damage signals and apoptotic pathways. Improved DNA repair capacity of ER-negative cells would have a growth advantage over ER-positive tumours when receiving antitumour therapy.
Skog
Sven
S
Department of Oncology Clinical Research Laboratory, KFC, Novum, Stockholm, Sweden. Sven.Skog@medhs.ki.se
He
Qimin
Q
Khoshnoud
Reza
R
Fornander
Tommy
T
Rutqvist
Lars-Erik
LE
D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006133:Growth Substances / Q000096:biosynthesis*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011960:Receptors, Estrogen / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D011960:Receptors, Estrogen