Studies on estrogen receptor (ER)-positive human breast cancer cell lines have shown that estrogen treatment positively modulates the expression of the genes encoding transforming growth factor-alpha (TGF alpha), 52-kDa cathepsin-D, and pS2.
Progestins both stimulate and inhibit breast cancer cell cycle progression while increasing expression of transforming growth factor alpha, epidermal growth factor receptor, c-fos, and c-myc genes.
Levels of TGF alpha and beta and EGFR mRNA were analysed in relationship to the relapse-free and overall survival of patients with breast cancer, but none was found to predict significantly the outcome in these patients.
Phorbol ester or epidermal growth factor (EGF) stimulates the concurrent accumulation of mRNA for the EGF receptor and its ligand transforming growth factor-alpha in a breast cancer cell line.
The abundance of TGF beta and TGF alpha mRNA in human breast cancer cell lines was not related directly to proliferation rate of the cells in culture or estrogen receptor positivity or negativity.
A clonogenic assay revealed that concentrations of TGF-alpha greater than 10(10) M induced a significant increase in colony formation, indicating TGF-alpha to be a breast cancer cell growth factor.
Transforming growth factors alpha and beta (TGF alpha and TGF beta) are two growth factors which are frequently associated with a number of human breast cancer cell lines and with primary human breast carcinomas.
To test this hypothesis we have introduced eukaryotic expression vectors directing the expression of TGF-alpha mRNA into E2-responsive MCF-7 human breast cancer cells.
Expression of transforming growth factor alpha and its messenger ribonucleic acid in human breast cancer: its regulation by estrogen and its possible functional significance.
Estrogen receptor (ER)-negative MDA-231 human breast cancer cells have been shown to secrete high concentrations of several growth factors including transforming growth factor-alpha and insulin-like growth factor I, which could have important autocrine or paracrine growth regulatory functions and, additionally, could explain the rapid autonomous growth of these cells.
We describe studies on human breast cancer in which it is shown that specific growth factors (IGF-I, TGF alpha, PDGF) are secreted by human breast cancer cells and likely to be involved in tumor growth and progression.
Breast cancer cell lines have been shown to secrete transforming growth factor alpha (TGF alpha) and other polypeptide growth factors in response to estrogen (E2) stimulation.
Transforming growth factor alpha (TGF alpha) and Transforming growth factor beta-1 (TGF-beta 1) are growth regulatory for breast cancer cell lines in vitro and several studies have suggested that levels of the receptor for TGF alpha, the epidermal growth factor (EGFR) in tumour biopsies predict relapse and survival.
To investigate the molecular mechanisms underlying the two- to three-fold induction of human transforming growth factor-alpha (hTGF-alpha) mRNA and two- to five-fold induction of hTGF-alpha protein observed following estrogen treatment of hormone-responsive human breast cancer cell lines, the hTGF-alpha promoter was assayed for ERE-like sequences able to mediate estrogen induction of a heterologous gene.
Epidermal growth factor and transforming growth factor alpha mRNA expression in human breast cancer biopsies; analysis in relation to estradiol, progesterone and EGF receptor content.
Non-virgin WAP-TGFalpha transgenic mice displayed accelerated mammary development during pregnancy, delayed post-parturient mammary involution, a progressive increase in the number of hyperplastic alveolar nodules (HANs), and development of mammary carcinoma with a mean latency of 9 months.
Typically, the progression of estrogen dependent primary breast cancers into a hormone-independent state, due to the loss of the estrogen receptor, is associated with increased levels of TGFalpha and EGFR, leading to aggressive breast carcinomas.
Targeted proteins, associated with different signal transduction pathways, have included transforming growth factor-alpha [TGF-alpha (MR(1))], its binding site the epidermal growth factor receptor [EGFR (MR(2))] sharing sequence homology to the breast cancer prognostic marker Her-2/neu, an apoptosis inhibiting protein [bcl-2 (MR(4))], and the androgen receptor [AR (MR(5))].
Our findings show some similarities between primary culture and breast cancer cell lines, but also some important differences: a) induction of TGF-alpha, a mitogenic protein, by TAM; b) a differential effect of TAM that may depend on relative expression of ER alpha and beta; and c) supraphysiological doses of T3 may induce mitogenic signals in breast cancer tissue under conditions of low circulating E2.
Moreover, we demonstrate that constitutive shedding of TGFα can be reduced by inhibition of Src in several cell lines, including COS7, MCF7 (the human breast cancer cell line), PAE (a pig aortic endothelial cell line) and HaCaT (the human keratinocyte cell line) cells.