Using Northern analysis and ribonuclease protection assays, IGF-II mRNA was detected in normal fibroblasts and in the established breast cancer cell line, T47D.
Additionally, both IGF-I and IGF-II mRNAs are easily detected in the majority of breast tumor specimens examined, while no breast cancer epithelial cell lines we have studied express authentic IGF-I mRNA, and few lines express IGF-II mRNA.
Autocrine production of insulin-like growth factor II using an inducible expression system results in reduced estrogen sensitivity of MCF-7 human breast cancer cells.
We have studied the regulation by estradiol of the mannose-6-phosphate (Man-6-P)/insulin-like growth factor-II (IGF-II) receptor concentration in different breast cancer cell lines.
This model demonstrates that IGF-II can serve as an autocrine growth stimulant in breast cancer epithelial cells and that IGF-II overexpression may be capable of mediating malignant progression in human breast cancer.
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.
Insulin-like growth factor-II (IGF-II) is a potent mitogen for a variety of cell types and is considered an important regulator of breast cancer growth.
These results demonstrate that hormonal changes associated with pregnancy accelerate breast cancer cell proliferation in the DMBA-induced MT model and suggest that this acceleration is mediated by up-regulation of IGF-II expression within neoplasms.
Despite the fact that expression of IGF-II was inversely related to several histopathological features of malignancy, the clinical behaviour of breast cancer seemed to be independent of IGF-II expression.
Our finding of IGF-II and IGFBP-3 in association with unfavourable prognostic indicators of breast cancer suggests that IGFs may be involved in the progression of breast cancer.
Conclusively, aberrant imprinting of IGF2 in 30% of the breast cancer patients tested provides strong evidence that pathological loss or relaxation of IGF2 imprinting plays an important role in either tumorigenesis or cytokine dysregulation for breast cancer cells.
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.
Parallel transfections now performed into another oestrogen-dependent human breast cancer cell line (ZR-75-1) yielded three clones of transfected ZR-75-1 cells that produced levels of zinc-inducible IGFII mRNA and secreted mature IGFII protein similar to those found in the transfected MCF7 cells.
Abnormally high levels of IGF-II may alter this homeostasis, conferring on breast cancer cells an advantageous mechanism that promotes rapid growth, and may facilitate metastasis.
In summary, we present here quantitative data confirming that a subclass of breast cancer samples has elevated levels of IGF-II transcripts by the new competitive RT-PCR assay.
These preliminary results indicate that IGF-II expression in breast cancer is connected with two important regulators of breast cancer growth and differentiation.
The role of IGF-II in cancer cell growth was evaluated in LNCaP, PC3, and M12 prostate cancer cell lines and MCF-7 breast cancer cell line by ribozyme/antisense strategies which were previously shown to suppress endogenous IGF-II expression and cell growth in PC-3 cells [Xu et al., Endocrinol 140 (1999) 2134].