Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast cancer cells

Matthew J C Ellis, Brett A. Leav, Zejia Yang, Audrey Rasmussen, Amelia Pearce, James A. Zweibel, Marc E Lippman, Kevin J. Cullen

Research output: Contribution to journalArticle

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Abstract

We have investigated the autocrine regulation of insulin-like growth factor-II (IGF-II) signaling by the insulin-like growth factor-I receptor (IGF-IR) and the insulin-like growth factor-II/mannose 6-phosphate receptor (IGF-IIR) in MCF-7 breast cancer cells, employing retroviruses encoding both IGF-I, IGF-II, and IGF-I and II mutants with reductions in affinity for either the IGF-IR or the IGF-IIR. These studies revealed reciprocal roles for IGF-IR and IGF-IIR affinity in the regulation of autocrine IGF-II activity. IGF-IR affinity was required for serum-free proliferation but also for efficient IGF-II secretion. In contrast, cellular proliferation, receptor tyrosine kinase-dependent signaling, and extracellular IGF-II protein accumulation were all reduced in the presence of IGF-IIR affinity. Inhibition of IGF-II signaling appeared to be the sole consequence of IGF-IIR affinity, as no cellular responses attributable to selective IGF-IIR binding by a reduced IGF-IR affinity IGF-II mutant could be detected. By operating as an IGF-II antagonist, the IGF-IIR has tumor suppressor-like properties, a suggestion consistent with reports of loss of heterozygosity at the IGF-IIR locus in a variety of human malignancies.

Original languageEnglish
Pages (from-to)286-297
Number of pages12
JournalMolecular Endocrinology
Volume10
Issue number3
DOIs
StatePublished - Mar 19 1996
Externally publishedYes

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IGF Type 2 Receptor
Insulin-Like Growth Factor II
Breast Neoplasms
IGF Type 1 Receptor
Insulin-Like Growth Factor I

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Ellis, M. J. C., Leav, B. A., Yang, Z., Rasmussen, A., Pearce, A., Zweibel, J. A., ... Cullen, K. J. (1996). Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast cancer cells. Molecular Endocrinology, 10(3), 286-297. https://doi.org/10.1210/me.10.3.286

Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast cancer cells. / Ellis, Matthew J C; Leav, Brett A.; Yang, Zejia; Rasmussen, Audrey; Pearce, Amelia; Zweibel, James A.; Lippman, Marc E; Cullen, Kevin J.

In: Molecular Endocrinology, Vol. 10, No. 3, 19.03.1996, p. 286-297.

Research output: Contribution to journalArticle

Ellis, MJC, Leav, BA, Yang, Z, Rasmussen, A, Pearce, A, Zweibel, JA, Lippman, ME & Cullen, KJ 1996, 'Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast cancer cells', Molecular Endocrinology, vol. 10, no. 3, pp. 286-297. https://doi.org/10.1210/me.10.3.286
Ellis, Matthew J C ; Leav, Brett A. ; Yang, Zejia ; Rasmussen, Audrey ; Pearce, Amelia ; Zweibel, James A. ; Lippman, Marc E ; Cullen, Kevin J. / Affinity for the insulin-like growth factor-II (IGF-II) receptor inhibits autocrine IGF-II activity in MCF-7 breast cancer cells. In: Molecular Endocrinology. 1996 ; Vol. 10, No. 3. pp. 286-297.
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