Transgenic Mammary Epithelial Osteopontin (spp1) Expression Induces Proliferation and Alveologenesis

Overview

Journal Genes Cancer

Specialty Oncology

Date 2013 Sep 27

PMID 24069507

Citations 12

Authors

Neil E Hubbard

Qian J Chen

Laura K Sickafoose

Meghan B Wood

Jeffrey P Gregg

Ninnie M Abrahamsson

Jesse A Engelberg

Judith E Walls

Alexander D Borowsky

Affiliations

Soon will be listed here.

Abstract

Osteopontin (OPN) Spp1 is involved in differentiation of the mammary gland. We engineered mice to overexpress OPN in mammary epithelium and describe an altered mammary phenotype. Three transgenic (Tg) founder lines FVB/N Tg(MMTV-Opn)((1-3BOR)) were propagated after FVB/NJ pronuclear injections. Mammary glands from Tg-OPN mice compared to littermate controls showed, at 4 weeks of age, exaggerated terminal end buds; at 8 and 12 weeks, more numerous and complex ducts with increased luminal protein; and at 16 weeks, increased lobulogenesis. Lactational Tg-OPN mammary glands showed more rapid lobulogenesis and lactational changes with slower gland involution and regression following weaning. Ex vivo lobulogenesis was noticeably increased from organoids of Tg-OPN mice. Immunohistochemistry revealed cytoplasmic OPN accumulation and increased Ki-67 positive mammary epithelial cells in Tg-OPN mammary glands. OPN appears to convey a proliferative stimulus for mammary epithelial cells and alters development and differentiation. These OPN mammary overexpressing mice provide a means to study the role of OPN in cancer progression.

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