Jena Manoj Kumar, Jaswal Shalini, Kumar Sudarshan, Mohanty Ashok Kumar
Animal Biotechnology Centre, National Dairy Research Institute (NDRI), Karnal 132001, India; Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University (LPU), Phagwara 144411, Punjab, India.
Animal Biotechnology Centre, National Dairy Research Institute (NDRI), Karnal 132001, India.
Dev Biol. 2019 Jan 15;445(2):145-155. doi: 10.1016/j.ydbio.2018.11.002. Epub 2018 Nov 15.
The mammary gland (MG) is a unique organ responsible for milk synthesis, secretion, and involution to prepare the gland for subsequent lactation. The mammary epithelial cells (MECs), which are the milk synthesizing units of the MG, proliferate, differentiate, undergo apoptosis and regenerate following a cyclic pathway of lactation - involution - lactation, fine-tuning these molecular events through hormones, growth factors and other regulatory molecules. The developmental stages of the MG are embryonic, prepubertal, pubertal, pregnancy, lactation and involution, with major developmental processes occurring after puberty. The involution stage includes interesting physiological processes such as MEC apoptosis, matrix remodeling, and the generation of cells regaining the shape of a virgin MG. Signal transducer and activator of transcription 3 (STAT3) is the established master regulator of this process and aberrant expression of STAT3 leads to subnormal involution and may induce neoplasia. Several studies have reported on the molecular mechanism of MG involution with substantial knowledge being gained about this process; however, a deep understanding of this phenomenon has yet to be attained. This review focuses deeply on the molecular details of post-lactational regression, the signaling pathways involved in the lactation-involution cycle, and the latest developments in STAT3-associated MG neoplasia. Deep insight into the involution process will pave the way towards understanding the biology, apoptosis, and oncogenesis of the MG.
乳腺（MG）是一个独特的器官，负责乳汁的合成、分泌和退化，为后续哺乳做好腺体准备。乳腺上皮细胞（MECs）是MG的乳汁合成单位，它们在泌乳 - 退化 - 泌乳的循环途径中增殖、分化、经历凋亡并再生，通过激素、生长因子和其他调节分子对这些分子事件进行微调。MG的发育阶段包括胚胎期、青春期前、青春期、怀孕期、哺乳期和退化期，主要发育过程发生在青春期之后。退化期包括一些有趣的生理过程，如MEC凋亡、基质重塑以及细胞恢复处女型MG形态的过程。信号转导和转录激活因子3（STAT3）是这一过程公认的主要调节因子，STAT3的异常表达会导致退化不完全，并可能诱发肿瘤形成。多项研究报道了MG退化的分子机制，对这一过程也有了相当多的了解；然而，对这一现象的深入理解尚未实现。本综述深入关注产后退化的分子细节、泌乳 - 退化周期中涉及的信号通路以及与STAT3相关的MG肿瘤形成的最新进展。对退化过程的深入了解将为理解MG的生物学、凋亡和肿瘤发生铺平道路。
