Expression of a prolactin-like factor in preneoplastic and neoplastic mouse mammary gland and cells

ABSTRACT Prolactin is a member of the growth hormone family and is required for the growth and terminal differentiation of the mammary gland. Ectopic production of this hormone has been reported in several species, including rat, sheep, goat and human mammary tissues. In this study, mouse mammary cell lines, xenographs in the mammary gland from these cell lines and from hyperplastic alveolar nodules, spontaneous tumors, and normal tissues were studied for de novo production of this growth factor. Prolactin transcripts were found by reverse transcriptase PCR in some neoplastic and preneoplastic tissues and in mouse mammary cell lines, NOG8 and CDNR4, but were not detected in the normal mouse mammary gland. Northern analysis revealed a 1 kb transcript for both cell lines that co-migrated with the prolactin pituitary transcript. Conditioned medium from NOG8 cells was positive for prolactin bioactivity by the Nb2 rat lymphoma cell proliferation assay, and Western analysis revealed the presence of immunoreactive proteins at Mr 14 000 and 60 000. Prolactin-like bioactivity was not detected in conditioned medium from CDNR4 cells, but an immunoreactive protein of Mr 60 000 was detected by Western analysis. The mouse mammary cell line, Comma D, was negative for prolactin transcripts; however, adenocarcinomas derived from inoculation of Comma D cells into the cleared mammary fat pad were positive by reverse transcriptase PCR in two of four cases. Hyperplastic outgrowths maintained in the cleared mammary fat pad as well as spontaneous tumors were positive for prolactin transcripts in one of four cases. These results suggest that prolactin can be produced ectopically by the neoplastic mouse mammary gland.

Download Full-text

Aryl hydrocarbon hydroxylase in mouse mammary gland: In vitro study using mammary cell lines

Chemico-Biological Interactions ◽

10.1016/0009-2797(77)90067-9 ◽

1977 ◽

Vol 17 (1) ◽

pp. 9-16 ◽

Cited By ~ 6

Author(s):

A.H.L. Chuang ◽

E.F. Howard ◽

E. Bresnick

Keyword(s):

Mammary Gland ◽

Cell Lines ◽

In Vitro Study ◽

Mouse Mammary Gland ◽

Vitro Study ◽

Aryl Hydrocarbon Hydroxylase ◽

Aryl Hydrocarbon ◽

Mammary Cell

Download Full-text

Long Intergenic Non-Coding RNAs in the Mammary Parenchyma and Fat Pad of Pre-Weaning Heifer Calves: Identification and Functional Analysis

Animals ◽

10.3390/ani11051268 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1268

Author(s):

Shengchao Zhang ◽

Sibtain Ahmad ◽

Yuxia Zhang ◽

Guohua Hua ◽

Jianming Yi

Keyword(s):

Mammary Gland ◽

Crude Protein ◽

Regulatory Mechanism ◽

Differentially Expressed ◽

Milk Replacer ◽

Rna Seq ◽

Fat Pad ◽

Mammary Fat Pad ◽

Non Coding Rnas ◽

Gland Development

Enhanced plane of nutrition at pre-weaning stage can promote the development of mammary gland especially heifer calves. Although several genes are involved in this process, long intergenic non-coding RNAs (lincRNAs) are regarded as key regulators in the regulated network and are still largely unknown. We identified and characterized 534 putative lincRNAs based on the published RNA-seq data, including heifer calves in two groups: fed enhanced milk replacer (EH, 1.13 kg/day, including 28% crude protein, 25% fat) group and fed restricted milk replacer (R, 0.45 kg/day, including 20% crude protein, 20% fat) group. Sub-samples from the mammary parenchyma (PAR) and mammary fat pad (MFP) were harvested from heifer calves. According to the information of these lincRNAs’ quantitative trait loci (QTLs), the neighboring and co-expression genes were used to predict their function. By comparing EH vs R, 79 lincRNAs (61 upregulated, 18 downregulated) and 86 lincRNAs (54 upregulated, 32 downregulated) were differentially expressed in MFP and PAR, respectively. In MFP, some differentially expressed lincRNAs (DELs) are involved in lipid metabolism pathways, while, in PAR, among of DELs are involved in cell proliferation pathways. Taken together, this study explored the potential regulatory mechanism of lincRNAs in the mammary gland development of calves under different planes of nutrition.

Download Full-text

Participation of two different mesenchymes in the developing mouse mammary gland: synthesis of basement membrane components by fat pad precursor cells

Development ◽

10.1242/dev.89.1.243 ◽

1985 ◽

Vol 89 (1) ◽

pp. 243-257

Author(s):

Koji Kimata ◽

Teruyo Sakakura ◽

Yutaka Inaguma ◽

Masato Kato ◽

Yasuaki Nishizuka

Keyword(s):

Extracellular Matrix ◽

Mammary Gland ◽

Flank Region ◽

Mouse Mammary Gland ◽

Precursor Cells ◽

Basement Membranes ◽

Immunofluorescent Staining ◽

Fat Pad ◽

Matrix Products ◽

Membrane Components

Two different types of mesenchyme, fat pad precursor cells (FP) and fibroblastic cells (MM) are involved in the morphogenesis of mammary gland epithelium of mouse embryo. Especially, an interaction between FP and the epithelium is necessary for its characteristic shaping of ductal branching structure. To assess the relative participations of the mesenchymes, we have analysed the extracellular matrix products by immunofluorescent staining method using antibodies to laminin, proteoheparan sulphate, and fibronectin. The staining patterns suggested that, after the 16th day of gestation when fatty substances first appeared in FP and the epithelial rudiments started to elongate and branch rapidly, FP initiated synthesis of laminin and proteoheparan sulphate, while MM synthesized fibronectin at all times. Attention was also paid to differences in the epithelial basement membranes (BM) concomitant with ones in the mesenchyme. BM were always stained with antibodies to laminin and proteoheparan sulphate. However, topographical differences in thickness were observed: the one facing FP, often seen at the tip region of the end bud, was thin, while the other surrounded by MM, often at the flank region of the duct, was thick. Specific elaboration of BM-like extracellular matrix products by FP may attribute to observed differences in BM thickness which are related to the characteristic shaping of the mammary gland.

Download Full-text

Prolactin affects leptin action in the bovine mammary gland via the mammary fat pad

Journal of Endocrinology ◽

10.1677/joe.1.06913 ◽

2006 ◽

Vol 191 (2) ◽

pp. 407-413 ◽

Cited By ~ 22

Author(s):

Y Feuermann ◽

S J Mabjeesh ◽

L Niv-Spector ◽

D Levin ◽

A Shamay

Keyword(s):

Mammary Gland ◽

Epithelial Cells ◽

Endocrine System ◽

Metabolic Adaptation ◽

Bovine Mammary Gland ◽

Fat Pad ◽

Metabolic Hormones ◽

Mammary Fat Pad ◽

Nutrient Partitioning ◽

Energy Consuming

One of the roles of the endocrine system is to synchronize mammary function. Hormones, such as estrogen, progesterone, and prolactin act directly on the mammary gland. Metabolic hormones, such as GH, glucocorticoids, insulin, and leptin are responsible for coordinating the body’s response to metabolic homeostasis. Leptin has been shown to be an important factor in regulating the metabolic adaptation of nutrient partitioning during the energy-consuming processes of lactation. In the present study, we show that leptin is secreted from the mammary fat, and is regulated by prolactin. The expression of α-casein in a co-culture of epithelial cells and fat explants was enhanced by prolactin compared with that in epithelial cells cultured alone. Leptin antagonist abolished the effect of leptin on α-casein expression in mammary gland explants when exogenous leptin was not present in the medium. This finding supports our hypothesis that the antagonist abolishes the action of endogenous leptin secreted by the mammary adipocytes. These results lead us to the hypothesis that prolactin and leptin act in the bovine mammary gland, via mammary fat pad/adipocytes.

Download Full-text

Site-specific inductive and inhibitory activities of MMP-2 and MMP-3 orchestrate mammary gland branching morphogenesis

The Journal of Cell Biology ◽

10.1083/jcb.200302090 ◽

2003 ◽

Vol 162 (6) ◽

pp. 1123-1133 ◽

Cited By ~ 182

Author(s):

Bryony S. Wiseman ◽

Mark D. Sternlicht ◽

Leif R. Lund ◽

Caroline M. Alexander ◽

Joni Mott ◽

...

Keyword(s):

Mammary Gland ◽

Branching Morphogenesis ◽

Mammary Epithelial ◽

Fat Pad ◽

Point Selection ◽

Site Specific ◽

Lateral Branching ◽

Mammary Fat Pad ◽

Epithelial Cell Apoptosis ◽

Inhibitory Activities

During puberty, mouse mammary epithelial ducts invade the stromal mammary fat pad in a wave of branching morphogenesis to form a complex ductal tree. Using pharmacologic and genetic approaches, we find that mammary gland branching morphogenesis requires transient matrix metalloproteinase (MMP) activity for invasion and branch point selection. MMP-2, but not MMP-9, facilitates terminal end bud invasion by inhibiting epithelial cell apoptosis at the start of puberty. Unexpectedly, MMP-2 also represses precocious lateral branching during mid-puberty. In contrast, MMP-3 induces secondary and tertiary lateral branching of ducts during mid-puberty and early pregnancy. Nevertheless, the mammary gland is able to develop lactational competence in MMP mutant mice. Thus, specific MMPs refine the mammary branching pattern by distinct mechanisms during mammary gland branching morphogenesis.

Download Full-text

The Cleared Mammary Fat Pad and the Transplantation of Mammary Gland Morphological Structures and Cells

Methods in Mammary Gland Biology and Breast Cancer Research ◽

10.1007/978-1-4615-4295-7_6 ◽

2000 ◽

pp. 67-74 ◽

Cited By ~ 24

Author(s):

Lawrence J. T. Young

Keyword(s):

Mammary Gland ◽

Fat Pad ◽

Mammary Fat Pad

Download Full-text

Evidence That the Mammary Fat Pad Mediates the Action of Growth Hormone in Mammary Gland Development

Endocrinology ◽

10.1210/endo.139.2.5718 ◽

1998 ◽

Vol 139 (2) ◽

pp. 659-662 ◽

Cited By ~ 53

Author(s):

Paul D. Walden ◽

Weifeng Ruan ◽

Mark Feldman ◽

David L. Kleinberg

Keyword(s):

Growth Hormone ◽

Mammary Gland ◽

Mammary Gland Development ◽

Fat Pad ◽

Mammary Fat Pad ◽

Gland Development

Download Full-text

Peroxisomal membrane channel Pxmp2 in the mammary fat pad is essential for stromal lipid homeostasis and for development of mammary gland epithelium in mice

Developmental Biology ◽

10.1016/j.ydbio.2014.03.022 ◽

2014 ◽

Vol 391 (1) ◽

pp. 66-80 ◽

Cited By ~ 9

Author(s):

Miia H. Vapola ◽

Aare Rokka ◽

Raija T. Sormunen ◽

Leena Alhonen ◽

Werner Schmitz ◽

...

Keyword(s):

Mammary Gland ◽

Lipid Homeostasis ◽

Fat Pad ◽

Membrane Channel ◽

Peroxisomal Membrane ◽

Mammary Fat Pad

Download Full-text

125 ISOLATION OF MULTILINEAGE STEM CELLS FROM THE PORCINE MAMMARY FAT PAD

Reproduction Fertility and Development ◽

10.1071/rdv18n2ab125 ◽

2006 ◽

Vol 18 (2) ◽

pp. 171

Author(s):

T. Davidson ◽

S. Lane ◽

C. Ferguson ◽

M. Wheeler ◽

W. Hurley

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Mammary Gland ◽

Calf Serum ◽

Cell Types ◽

Tissue Type ◽

Mammary Tissue ◽

Adipose Derived Stem Cells ◽

Fat Pad ◽

Mammary Fat Pad

Porcine mammary tissue is a dynamic system that undergoes multiple cycles of growth, differentiation, and regression during the life cycle of a female; however, the mechanisms of mammary morphogenesis are not fully understood. The current hypothesis suggests that epithelial stem cells in the terminal end buds interact with surrounding epithelial and stromal cells during mammary tissue development and regeneration. Because the mammary gland of the virgin animal consists largely of a pad of adipose tissue, we propose that adipose-derived stem cells from the mammary fat pad (MFP) may also play a role in the regeneration process. Therefore, the objective of this experiment was to determine whether multilineage stem cells are present in the MFP of gilts. Adipose tissue from the MFP and back fat (BF) from the loin region were harvested from six nulliparous, cycling Yorkshire gilts, approximately 16 mo of age. Methods for isolation of adipose-derived stem cells were modified from those of Malusky and Wheeler (2004; International Society for Stem Cell Research, Proceedings 2nd Annual Meeting, abstr. 248:124). Presumptive stem cells isolated from each tissue type were maintained in vitro in DMEM supplemented with either 10% newborn calf serum (NCS; Rep 1 and 2) or 10% fetal calf serum (Rep 3). BF and MFP cell types formed colonies of fibroblast-like cells within 3 to 5 d. Growth characteristics are shown in Table 1. When the cells were 80% confluent, they were trypsinized and reseeded into 75-cm2 flasks. When cultured in the presence of NCS, both cell types had a progressive decrease in viability, and these cultures could not be maintained past Passage 4. Differentiation of both cell types (Passage 1) into adipogenic, myogenic, and osteogenic lineages are currently underway. Based on morphological evaluations, both cell types are able to differentiate into the aforementioned lineages; however, differentiation of MFP-derived cells occurred at a slower rate and was less pronounced than that of BF-derived cells. These preliminary findings suggest that the MFP likely contains a population of multipotent stem cells; however, at this time, it is not possible to make meaningful statistical comparisons. Further experiments are needed to fully characterize these cells and determine their role in mammary gland morphogenesis. Table 1. Growth of porcine adipose-derived stem cells obtained from the BF or from the MFP This study was partially supported by the Council for Food and Agricultural Research (C-FAR) Sentinel Program and USDA Multistate Project (W-1171).

Download Full-text