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Pituitary. 2011 Mar;14(1):44-52. doi: 10.1007/s11102-010-0257-0.

Pasireotide, an IGF-I action inhibitor, prevents growth hormone and estradiol-induced mammary hyperplasia.

Author information

1
The Bunnie Joan Sachs Laboratory and Neuroendocrine Unit, Department of Medicine (Division of Endocrinology), New York University School of Medicine, New York, NY, USA. David.Kleinberg@nyumc.org

Abstract

Mammary hyperplasia increases breast cancer risk. Tamoxifen prevents breast cancer in women with atypical hyperplasia, but has serious side effects. As estradiol action requires IGF-I, direct inhibition of IGF-I action theoretically might be an efficacious alternative to tamoxifen. After hypophysectomy and oophorectomy, 21-day-old female rats were treated with GH and E₂. After 7 days all terminal end buds (TEBs) and 75% of ducts became hyperplastic. Co-treatment with pasireotide, a somatostatin analog that blocks GH secretion and IGF-I action in the mammary gland, prevented hormone-induced hyperplasia. The number and size of TEBs and moderately or floridly hyperplastic ducts was reduced by pasireotide (P < 0.01). In contrast, the same concentration of octreotide, which has a more selective somatostatin receptor subtype binding profile, was less effective than pasireotide. Tamoxifen inhibited hyperplasia when used alone with GH + E₂, but did not add to the inhibitory effect of pasireotide when the two treatments were combined. Both pasireotide and tamoxifen acted via the IGF-I receptor signaling pathway and both were found to inhibit mammary cell proliferation and stimulate apoptosis. The number of epithelial cells expressing phosphorylated insulin receptor substrate (IRS)-1 in response to GH and E₂ was reduced by pasireotide, as was staining intensity. These results support the concept that IGF-I inhibition, in this case by pasireotide, inhibits E₂ and GH-induced mammary hyperplasia. As tamoxifen did not further increase the inhibitory effect of pasireotide, the peptide appears to be at least as effective as tamoxifen in preventing GH + E₂-induced mammary hyperplasia.

PMID:
20890664
DOI:
10.1007/s11102-010-0257-0
[Indexed for MEDLINE]

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