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The growth hormone receptor antagonist pegvisomant blocks both mammary gland development and MCF-7 breast cancer xenograft growth.
- Source :
- Breast Cancer Research & Treatment; Aug2006, Vol. 98 Issue 3, p315-327, 13p
- Publication Year :
- 2006
-
Abstract
- <span class="AbstractHeading">Summary  </span>Mammary gland development is dependent upon the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis, this same axis has also been implicated in breast cancer progression. In this study we investigated the effect of a GH antagonist, pegvisomant (Somavert<superscript>®</superscript>, Pfizer), on normal mammary gland development and breast cancer xenograft growth. Intraperitoneal administration of pegvisomant resulted in a 60% suppression of hepatic IGF-I mRNA levels and upto a 70–80% reduction of serum IGF-I levels. Pegvisomant administration to virgin female mice caused a significant delay of mammary ductal outgrowth that was associated with a decrease in the number of terminal end buds and reduced branching and complexity of the gland. This effect of pegvisomant was mediated by a complete inhibition of both GH and IGF-IR-mediated signaling within the gland. In breast cancer xenograft studies, pegvisomant caused shrinkage of MCF-7 xenografts, with an initial 30% reduction in tumor volume, which was associated with a 2-fold reduction in proliferation and a 2-fold induction of apoptosis. Long-term growth inhibition of MCF-7 xenografts was noted. In contrast, pegvisomant had no effect on MDA-231 or MDA-435 xenografts, consistent with primary growth of these xenografts being unresponsive to IGF-I both in vitro and in vivo. In MCF-7 xenografts that regressed, pegvisomant had only minor effects upon GHR and IGF-IR signaling. This data supports previous studies indicating a role for GH/IGF in mammary gland development, and suggests that pegvisomant maybe useful for the prevention and/or treatment of estrogen receptor positive breast cancer. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01676806
- Volume :
- 98
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Breast Cancer Research & Treatment
- Publication Type :
- Academic Journal
- Accession number :
- 21875179
- Full Text :
- https://doi.org/10.1007/s10549-006-9168-1