Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, P.R. China.
Sci Rep. 2019 Oct 8;9(1):14436. doi: 10.1038/s41598-019-50819-4.
p21-activated kinases (PAKs) are serine/threonine kinases functioning as downstream effectors of the small GTPases Rac1 and Cdc42. Members of the PAK family are overexpressed in human breast cancer, but their role in mammary gland development is not fully explored. Here we examined the functional role of PAK4 in mammary gland development by creating a mouse model of MMTV-Cre driven conditional PAK4 gene depletion in the mammary gland. The PAK4 conditional knock-out mice were born healthy, with no observed developmental deficits. Mammary gland whole-mounts revealed no defects in ductal formation or elongation of the mammary tree through the fat pad. PAK4 gene depletion also did not alter proliferation and invasion of the mammary epithelium in young virgin mice. Moreover, adult mice gave birth to healthy pups with normal body weight upon weaning. This implies that MMTV-Cre induced gene depletion of PAK4 in mice does not impair normal mammary gland development and thereby provides an in vivo model that can be explored for examination of the potential function of PAK4 in breast cancer.
p21 激活激酶 (PAKs) 是丝氨酸/苏氨酸激酶，作为小 GTPases Rac1 和 Cdc42 的下游效应物发挥作用。PAK 家族成员在人类乳腺癌中过表达，但它们在乳腺发育中的作用尚未完全探索。在这里，我们通过创建一种 MMTV-Cre 驱动的乳腺中 PAK4 基因条件缺失的小鼠模型，研究了 PAK4 在乳腺发育中的功能作用。PAK4 条件敲除小鼠出生健康，没有观察到发育缺陷。乳腺全培养揭示了乳腺树通过脂肪垫形成和伸长的导管形成或伸长没有缺陷。PAK4 基因缺失也没有改变年轻处女小鼠乳腺上皮细胞的增殖和侵袭。此外，成年小鼠在断奶时产下了健康的幼仔，体重正常。这意味着 MMTV-Cre 诱导的 PAK4 基因缺失在小鼠中不会损害正常的乳腺发育，并因此提供了一种体内模型，可以用于研究 PAK4 在乳腺癌中的潜在功能。
