Nevertheless, IGF-I mRNA can be detected in breast cancer tissue samples, and in situ hybridization studies have shown that the message originates from the stromal cells adjacent to normal lobules.
We have identified and characterized a novel human insulin-like growth factor I (IGF-I) precursor from the transplantable T61 human breast cancer xenograft and from normal liver.
We conclude that type I and type II IGF receptors are ubiquitously expressed in breast cancer, and our experiments with MCF-7 cells suggest the mitogenic effects of both IGF-I and IGF-II are mediated via the type I IGF receptor.
IGF-I and estradiol had similar synergistic effects on other estrogen-responsive breast cancer cell lines, but IGF-I alone increased the proliferation of the MDA MB-231 cell line which is not responsive to estrogens.
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.
We have analyzed the stromal mRNA expression of IGF-I and IGF-II in matched sets of fibroblast cell lines derived from three locations in the affected breast of eight patients with breast cancer: (a) the breast tumor itself; (b) surrounding normal breast tissue; and (c) overlying breast skin.
Expression of receptors for epidermal growth factor and insulin-like growth factor I by ZR-75-1 human breast cancer cell variants is inversely related: the effect of steroid hormones on insulin-like growth factor I receptor expression.
Both the insulin and IGF-I receptors (IGF-IR) are overexpressed in breast cancer, and antibody blockade of the IGF-IR inhibits the growth of some breast cancer cell lines.
Four lines of evidence lead us to conclude that E2 induces BRCA1 primarily through an increase in DNA synthesis: (1) The kinetics and magnitude of induction are different from the directly E2 inducible gene, pS2; (2) Induction of BRCA1, but not pS2, is blocked by cycloheximide indicating that de novo protein synthesis is required; (3) Other hormonal and growth factor treatments that induce DNA synthesis have a similar effect, including IGF-1, EGF and DNA synthetic flares induced by tamoxifen and retinoic acid; (4) BRCA1 genomic fragments near the 5' end of the gene containing putative estrogen response elements fail to respond to E2 when transfected into breast cancer cell lines.
This case-control study was designed to investigate whether patients with breast cancer have altered levels of either IGF-1 or its intermediary modulatory proteins, the IGF binding proteins (BP).
Expression of mRNA encoding for IGF-1, IGF-2, IGF-receptor 1 and 2, IGF binding proteins- 1 to -6, insulin receptor and insulin was determined in the NIH MCF-7 breast cancer cell line, in specimens from breast cancer tissues, and in 6 primary breast cancer cell cultures obtained from metastatic breast cancer, using rT-PCR technique.
Insulin-like growth factors I and II (IGF-I and IGF-II) are potent mitogens involved in growth regulation of breast epithelial cells and are implicated in the pathophysiology of breast cancer.
By linking IGFBP-3 to RARbeta, our experiments define the signal intersection between the retinoid and IGF systems in cell growth regulation and explain why loss of RARbeta might be critical in breast cancer carcinogenesis/progression.