Amphiregulin as an autocrine growth factor for c-Ha-ras- and c-erbB-2-transformed human mammary epithelial cells.
- 29 March 1994
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 91 (7) , 2790-2794
- https://doi.org/10.1073/pnas.91.7.2790
Abstract
Amphiregulin (AR), a member of the epidermal growth factor (EGF) family, was found to be as potent as EGF in stimulating the anchorage-dependent growth (ADG) of immortalized, nontransformed human mammary epithelial MCF-10A cells. MCF-10A cells transformed by either an activated human c-Ha-ras protooncogene (MCF-10A ras) or by overexpression of a nonactivated rat c-neu gene (MCF-10A neu) exhibited a 35% reduction in the response to AR in ADG when compared to MCF-10A cells, but AR was still as potent as EGF in these transformants. Exogenous AR exhibited only 15-20% of the activity of EGF in stimulating the anchorage-independent growth, a response that is normally dependent upon exogenous EGF, of the oncogene-transformed MCF-10A cells. MCF-10A cells express low levels of a 1.4-kb AR mRNA transcript, while MCF-10A ras and MCF-10A neu cells display a 15- to 30-fold increase in the levels of AR mRNA and endogenous AR protein as determined by Western blot analysis. Exogenous EGF was found to induced both the AR mRNA and protein in the MCF-10A parental and transformed cells. A 20-mer phosphorothioate antisense deoxyoligonucleotide complementary to the 59 sequence of AR mRNA was able to significantly reduce the levels of endogenous AR protein and to inhibit the EGF-stimulated ADG and anchorage-independent growth of MCF-10A ras and MCF-10A neu cells. These data suggest that AR may function as an EGF-dependent autocrine growth factor in mammary epithelial cells that have been transformed by either a point-mutated c-Ha-ras or c-neu.Keywords
This publication has 27 references indexed in Scilit:
- Heparin inhibition of autonomous growth implicates amphiregulin as an autocrine growth factor for normal human mammary epithelial cellsJournal of Cellular Physiology, 1992
- Autocrine action of amphiregulin in a colon carcinoma cell line and immunocytochemical localization of amphiregulin in human colon.The Journal of cell biology, 1992
- A dual receptor system is required for basic fibroblast growth factor activityCell, 1991
- Epidermal growth factor and transforming growth factor-alpha: differential intracellular routing and processing of ligand-receptor complexes.Cell Regulation, 1991
- c‐erbB‐2 and ras expression levels in breast cancer are correlated and show a co‐operative association with unfavorable clinical outcomeInternational Journal of Cancer, 1991
- Intracrine regulation at the nucleus–a further mechanism of growth factor activity?Journal of Endocrinology, 1990
- Epidermal growth factor and transforming growth factor-alpha induce differential processing of the epidermal growth factor receptorBiochemical and Biophysical Research Communications, 1990
- Structure and Function of Human Amphiregulin: A Member of the Epidermal Growth Factor FamilyScience, 1989
- Expression of p21ras gene products in breast cancer relates to histological types and to receptor and nodal statusBreast Cancer Research and Treatment, 1988
- Transforming growth factor αCell, 1988