Identification of genes involved in growth inhibition of breast cancer cells transduced with estrogen receptor

Abstract

Estrogen receptor K K (ERK K)-negative breast cancer cells display an aggressive phenotype. We previously showed that adenoviral expression of ERK K in ER-negative breast cancer cells leads to an estrogen-dependent down-regulation of the proliferation, which could be of interest to control the growth of such cells. In this study, we observed an increase in protein levels of p21 and p27 cyclin-dependent kinase inhibitors, whereas pRb phosphorylation is strongly decreased. Flow cytometry experiments showed a slower transit of cells in G1 (hormoneindependent), a hormone-induced accelerated transit through S phase and a possible arrest in G2/M phase. In addition, ERK Kexpressing cells were undergoing apoptosis. By using cDNA macroarrays, we identi¢ed a novel collection of genes regulated by liganded ERK K potentially regulating cell cycle, apoptosis, cell signalling, stress response and DNA repair.

ERβ is a potent inhibitor of cell proliferation in the HCT8 human colon cancer cell line through regulation of cell cycle components

“…Moreover, the use of a model that lacks ERa expression makes it possible to state that cyclin E regulation is due to a direct action of ERb repressing the activity of the cyclin E promoter. Furthermore, induction of p21CIP1 expression represents an additional mechanism through which ERb controls the colon cancer cell cycle, as the protein is essential in mammary cancer cells for growth and cell cycle arrest (Carroll et al 2002, Licznar et al 2003. Indeed, alteration in the expression of these proteins is sufficient to induce a G1-S cell cycle arrest in this cell model.…”

Estrogen receptor β inhibits 17β-estradiol-stimulated proliferation of the breast cancer cell line T47D

“…The importance of cyclin D1 expression is illustrated by studies indicating that the major antiproliferative effect of tamoxifen is related to its inhibition of cyclin D1 expression (11) and that overexpression of cyclin D1 or c-Myc is sufficient to increase the proliferation of MCF-7 cells (23). However, this is not the case in all situations: when ER␣ was expressed from an adenovirus vector in the breast cancer cell line MDA-MB-231, there was increased expression of cyclin D1 but a reduction in proliferation (24).…”

Concordance of HER-2/Neu over Expression with Steroid Receptor Status in Female Breast Cancers

“…No much correlation exists between the cytoarchitectural type of breast carcinoma and presence of hormone receptor protein, no statistically significant difference has been found between ductal type and lobular type tumors [5]. Because the growth of breast cancer is often regulated by the female sex steroids, the determinations of the cellular concentrations of ER and PR in the tumor are currently used to predict which patients are of good prognosis as they may also benefit from antihormonal therapy [6]. The ER cannot be clearly classified as an oncoprotein or tumor suppressor protein, although it clearly mediates onset and progression of the disease.…”

“…In addition, 5% to 10% of the patients designated ER-negative appear to initially respond to endocrine therapy [6]. To improve the value of determination of the ER for tumor prognosis, the presence of the estrogen-regulated PR protein is now routinely determined.…”

“…The c-erb-B-2 proto-oncogene is located on 17q21, with intrinsic tyrosine kinase activity homologous to EGF receptor. It is amplified and/or over expressed in approximately 30% of human breast tumors [6]. Over expression is associated with increased tumor aggressiveness, increased rates of recurrence, and increased mortality in node positive patients, while the influence in node negative patients is more variable.…”