Amphiregulin as an autocrine growth factor for c-Ha-ras- and c-erbB-2-transformed human mammary epithelial cells

Nicola Normanno, Mouna P. Selvam, Chen Feng Qi, Toshiaki Saeki, Gibbes Johnson, Nancy Kim, Fortunato Ciardiello, Mohammed Shoyab, Gregory Plowman, Ralf Brandt, George Todaro, David S. Salomon

Research output: Contribution to journalArticle

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 induce both AR mRNA and protein hi the MCF-10A parental and transformed cells. A 20-mer phosphorothioate antisense deoxyoligonucleotide complementary to the 5′ 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 automne growth factor in mammary epithelial cells that have been transformed by either a point-mutated c-Ha-ras or c-neu.

Original languageEnglish
Pages (from-to)2790-2794
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number7
Publication statusPublished - Mar 29 1994

Keywords

  • Breast cancer
  • c-neu
  • Ha-ras

ASJC Scopus subject areas

  • General
  • Genetics

Fingerprint Dive into the research topics of 'Amphiregulin as an autocrine growth factor for c-Ha-ras- and c-erbB-2-transformed human mammary epithelial cells'. Together they form a unique fingerprint.

  • Cite this

    Normanno, N., Selvam, M. P., Qi, C. F., Saeki, T., Johnson, G., Kim, N., Ciardiello, F., Shoyab, M., Plowman, G., Brandt, R., Todaro, G., & Salomon, D. S. (1994). Amphiregulin as an autocrine growth factor for c-Ha-ras- and c-erbB-2-transformed human mammary epithelial cells. Proceedings of the National Academy of Sciences of the United States of America, 91(7), 2790-2794.