Oleic acid stimulates HC11 mammary epithelial cells proliferation and mammary gland development in peripubertal mice through activation of CD36-Ca2+ and PI3K/Akt signaling pathway

Yingying Meng; Jing Zhang; Cong Yuan; Fenglin Zhang; Qin Fu; Han Su; Xiaotong Zhu; Lina Wang; Ping Gao; Gang Shu; Qingyan Jiang; Songbo Wang

doi:10.18632/oncotarget.24204

Oleic acid stimulates HC11 mammary epithelial cells proliferation and mammary gland development in peripubertal mice through activation of CD36-Ca²⁺ and PI3K/Akt signaling pathway

Oncotarget. 2018 Jan 12;9(16):12982-12994. doi: 10.18632/oncotarget.24204. eCollection 2018 Feb 27.

Authors

Yingying Meng^{1

2}, Jing Zhang^{1

2}, Cong Yuan^{1

2}, Fenglin Zhang^{1

2}, Qin Fu^{1

2}, Han Su^{1

2}, Xiaotong Zhu^{1

2}, Lina Wang^{1

2}, Ping Gao^{1

2}, Gang Shu^{1

2}, Qingyan Jiang^{1

2}, Songbo Wang^{1

2}

Affiliations

¹ Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, P. R. China.
² National Engineering Research Center for Breeding Swine Industry and UBT Lipid Suite Functional Fatty Acids Research Center, South China Agricultural University, Guangzhou 510642, P. R. China.

Abstract

This study aimed to investigate the effects of oleic acid (OA), a monounsaturated fatty acid, on HC11 mammary epithelial cells proliferation and peripubertal mammary gland development and explore the underlying mechanisms. HC11 cells and C57BL/6J mice were treated with OA. HC11 proliferation, peripubertal mammary gland development, and the involvement of CD36 and PI3K/Akt were assessed. In vitro, 100 μM OA significantly promoted HC11 proliferation by increasing Cyclin D1/3 and PCNA expression and decreasing p21 expression. Meanwhile, OA enhanced CD36 expression, elevated [Ca²⁺]_i and activated PI3K/Akt signaling pathway. However, knockdown of CD36, chelation of [Ca²⁺]_i or inhibition of PI3K eliminated the OA-induced promotion of HC11 proliferation and change in proliferative markers expression. In vivo, peripubertal exposure to diet containing 2% OA stimulated mammary duct development, with increased terminal duct end (TDE) and ductal branch. Moreover, dietary OA increased the serum levels of IGF-1 and E2, enhanced the expression of CD36 and Cyclin D1, and activated PI3K/Akt pathway in mammary glands. In conclusion, OA stimulated HC11 cells proliferation and mammary gland development in peripubertal mice, which was associated with activation of CD36-[Ca²⁺]_i and PI3K/Akt signaling pathway. These data provided new insights into the stimulation of mammary gland development by dietary oleic acid.

Keywords: CD36-[Ca2+]i; PI3K/Akt; mammary gland development; oleic acid (OA); peripubertal mice.