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Series GSE5116

Query DataSets for GSE5116

Status

Public on Aug 10, 2006

Title

Genomic Pathways of 17-beta-Estradiol Induced Malignant Cell Transformation in Human Breast Epithelial Cells

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

The estrogen-dependence of breast cancer has long been recognized, however, the role of 17β-estradiol (E2) in cancer initiation was not known until we demonstrated that it induces complete neoplastic transformation of the human breast epithelial cells MCF-10F. E2-treatment of MCF-10F cells progressively induced high colony efficiency and loss of ductulogenesis in early transformed (trMCF) cells and invasiveness in Matrigel invasion chambers. The cells that
crossed the chamber membrane were collected and identified as bsMCF, and their subclones designated bcMCF, and the cells harvested from carcinoma formation in SCID mice designated caMCF. These phenotypes correlated with gene dysregulation during the progression of the
transformation. The highest number of dysregulated genes was observed in caMCF, being slightly lower in bcMCF, and lowest in trMCF. This order was consistent with the extent of chromosome aberrations (caMCF > bcMCF >>> trMCF). Chromosomal amplifications were found in 1p36.12-pter, 5q21.1-qter and 13q21.31-qter. Losses of the complete chromosome 4 and 8p11.21-23.1 were found only in tumorigenic cells. In tumor-derived cell lines, additional losses were found in 3p12.1-14.1, 9p22.1-pter and 18q11.21-qter. Functional profiling of dysregulated genes revealed progressive changes in the integrin signaling pathway, inhibition of apoptosis, acquisition of tumorigenic cell surface markers and epithelial-mesenchymal transition. In tumorigenic cells, the levels of E-cadherin, EMA, and various keratins were low and CD44E/CD24 were negative, whereas SNAI2, vimentin, S100A4, FN1, HRAS, TGFβ1 and
CD44H were high. The phenotypic and genomic changes triggered by estrogen exposure that lead normal cells to tumorigenesis confirm the role of this steroid hormone in cancer initiation.
Keywords: Cell type comparison

Overall design

Human MCF-10F cells were transformed by 70nM 17-beta-estradiol. The transformed cells were selected by Boyden chamber. The selected cells were injected into SCID mice and also cloned and expanded. The thus grown tumors were harvested for cell culture. Genomic DNA and total RNA were isolated from cell lines in each step for 100K SNP and gene expression microarray assay.

Contributor(s)

Huang Y, Fernadez SV, Goodwin S, Russo PA, Russo IH, Sutter TR, Russo J

Citation(s)

18056439

Submission date

Jun 21, 2006

Last update date

Mar 25, 2019

Contact name

Yong Huang

E-mail(s)

yh9fj@virginia.edu