Changes in oestrogen, progesterone and epidermal growth factor receptor concentrations and affinities during the oestrous cycle in the normal mammary gland and uterus of dogs

The epidermal growth factor receptor (ErbB) family and its ligands are essential for the regulation of multiple cellular processes required for mammalian reproduction. The objectives of this study were to investigate the expression and localisation of ErbB subtypes (ErbB1–4) and selected ligands, namely epidermal growth factor (EGF), amphiregulin (AREG) and neuregulin (NRG), in the cervix and vagina of cycling cows and to determine possible steroid hormone-dependence of their expression using immunohistochemistry. All four ErbBs and EGF, AREG and NRG proteins were found to be localised in the nucleus and cytoplasm of different cells in the cervix and vagina, and their expression differed during the oestrous cycle. During the follicular phase, in both the cervix and vagina, ErbB1, ErbB2, ErbB3, ErbB4 and EGF expression was higher in the luminal epithelium (LE) than in stromal and smooth muscle (SM) cells (P<0.05). During the luteal phase, the expression of ErbB1, ErbB3 and EGF in the LE was significantly different from that in stromal and SM cells in the cervix, whereas the expression of EGF and AREG differed in the vagina compared to the cervix (P<0.05). Throughout the oestrous cycle, in both the cervix and vagina, although ErbB2/human epidermal growth factor receptor 2 expression in the LE and SM cells was significantly higher than in the stromal cells (P<0.05), NRG expression was similar in the LE, stromal and SM cells (P>0.05). Overall, these results suggest that all four ErbBs and the EGF, AREG and NRG proteins may collectively contribute to several cellular processes in the bovine cervix and vagina during the oestrous cycle.

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Epidermal Growth Factor Receptor (EGFR) Signaling Is a Key Mediator of Hormone-Induced Leukocyte Infiltration in the Pubertal Female Mammary Gland

Endocrinology ◽

10.1210/en.2013-1933 ◽

2014 ◽

Vol 155 (6) ◽

pp. 2301-2313 ◽

Cited By ~ 12

Author(s):

Mark D. Aupperlee ◽

Yong Zhao ◽

Ying Siow Tan ◽

Jeffrey R. Leipprandt ◽

Jessica Bennett ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Mammary Gland ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Mammary Gland Development ◽

Dominant Role ◽

Growth Factor Receptor ◽

Eosinophil Recruitment ◽

Epidermal Growth ◽

Gland Development

It is well documented that macrophages and eosinophils play important roles in normal murine pubertal mammary gland development. Although it is accepted that estrogen (E) and progesterone (P) are key players in mammary gland development, the roles these hormones might play in regulating the actions of leukocytes in that process is an understudied area. We show here that P and E, respectively, induce unique, but overlapping, sets of proinflammatory and angiogenic cytokines and chemokines, in the pubertal female BALB/c mammary gland, as well as induce infiltration of macrophages and eosinophils to the mammary periepithelium. This extends earlier studies showing P induction of proinflammatory products in pubertal and adult mammary epithelial organoids and P-induced in vivo infiltration of leukocytes to the adult mammary periepithelium. Importantly, epidermal growth factor receptor-signaling, which is likely mediated by amphiregulin (Areg), a downstream mediator of E and P, is both necessary and sufficient for both E- and P-induced recruitment of macrophages and eosinophils to the pubertal mammary periepithelium. We further show that receptor activator of nuclear factor κB ligand (RANKL), although not sufficient of itself to cause macrophage and eosinophil recruitment, contributes to an optimal response to P. The potency of Areg is highlighted by the fact that it is sufficient to induce macrophage and eosinophil recruitment at levels equivalent to that induced by either E or P. Our finding of a dominant role for Areg in hormonally induced leukocyte recruitment to the pubertal mammary gland parallels its dominance in regulating ductal outgrowth and its role in P-induced proliferation in the pubertal gland.

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Effects of Ovariectomy and Prolactin on Mammary Gland Expressions of Transforming Growth Factor α and Epidermal Growth Factor Receptor mRNAs in Mice

ZOOLOGICAL SCIENCE ◽

10.2108/0289-0003(1998)15[525:eooapo]2.0.co;2 ◽

1998 ◽

Vol 15 (4) ◽

pp. 525-529

Author(s):

Hiroshi Nagasawa ◽

Yoshie Ikezaki ◽

Kazutoshi Yamamoto

Keyword(s):

Epidermal Growth Factor Receptor ◽

Mammary Gland ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Transforming Growth Factor ◽

Growth Factor Receptor ◽

Transforming Growth Factor Α ◽

Epidermal Growth ◽

Factor Α ◽

Receptor Mrnas

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Morphological and immunohistochemical characterization and molecular classification of spontaneous mammary gland tumors in macropods

Veterinary Pathology ◽

10.1177/03009858211069164 ◽

2022 ◽

pp. 030098582110691

Author(s):

Tu Chun Hsu ◽

Michael M. Garner ◽

Matti Kiupel

Keyword(s):

Epidermal Growth Factor Receptor ◽

Mammary Gland ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Mammary Tumors ◽

Mammary Carcinomas ◽

Her 2 ◽

Epidermal Growth

Mammary gland neoplasms in macropods are uncommonly reported, and the morphological and immunohistochemical characteristics are incompletely described. The goal of this study was to describe the morphologic features of macropod mammary neoplasms and to determine the molecular subtypes of mammary carcinomas using a panel of antibodies against estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2), p63, smooth muscle actin (SMA), and epidermal growth factor receptor (EGFR). Biopsy and necropsy specimens were examined from 21 macropods with mammary tumors submitted to Northwest ZooPath from 1996 to 2019. In accordance with the histologic classification of canine mammary tumors proposed by Goldschmidt and colleagues, tubulopapillary (2), tubular (10), and comedo-carcinomas (2), adenoma (1), lobular hyperplasia (3), fibroadenomatous hyperplasia (1), and mastitis (2) were diagnosed. Red kangaroos ( Osphranter rufus) were most commonly diagnosed with mammary carcinomas (79% of all carcinomas). Seven carcinomas had lymphovascular invasion and 2 also had pulmonary metastases. Six of these 7 carcinomas were classified as grade 3. Immunohistochemistry (IHC) for all antibodies was performed on 9/14 carcinomas, and partial IHC was performed for 3 cases. All 12 carcinomas were immunoreactive for PR, 5 for ER, 9 for EGFR, and none for Her-2. Five of the 9 mammary carcinomas with complete IHC data were classified as luminal A subtype, and 4 were normal-like subtype. Accurate classification of mammary tumors in macropods based on morphology, immunohistological characteristics, and molecular subtype may be helpful in guiding clinical management, prognosis, and potential therapeutic targets.

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