scholarly journals Apoptosis in the terminal endbud of the murine mammary gland: a mechanism of ductal morphogenesis

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 4013-4022 ◽  
Author(s):  
R.C. Humphreys ◽  
M. Krajewska ◽  
S. Krnacik ◽  
R. Jaeger ◽  
H. Weiher ◽  
...  

Ductal morphogenesis in the rodent mammary gland is characterized by the rapid penetration of the stromal fat pad by the highly proliferative terminal endbud and subsequent formation of an arborized pattern of ducts. The role of apoptosis in ductal morphogenesis of the murine mammary gland and its potential regulatory mechanisms was investigated in this study. Significant apoptosis was observed in the body cells of the terminal endbud during the early stage of mammary ductal development. Apoptosis occurred predominately in defined zones of the terminal endbud; 14.5% of the cells within three cell layers of the lumen were undergoing apoptosis compared to 7.9% outside this boundary. Interestingly, DNA synthesis in the terminal endbud demonstrated a reciprocal pattern; 21.1% outside three cell layers and 13.8% within. Apoptosis was very low in the highly proliferative cap cell laver and in regions of active proliferation within the terminal endbud. In comparison to other stages of murine mammary gland development, the terminal endbud possesses the highest level of programmed cell death observed to date. These data suggest that apoptosis is an important mechanism in ductal morphogenesis. In p53-deficient mice, the level of apoptosis was reduced, but did not manifest a detectable change in ductal morphology, suggesting that p53-dependent apoptosis is not primarily involved in formation of the duct. Immunohistochemical examination of the expression of the apoptotic checkpoint proteins, Bcl-x, Bax and Bcl-2, demonstrated that they are expressed in the terminal endbud. Bcl-x and Bcl-2 expression is highest in the body cells and lowest in the nonapoptotic cap cells, implying that their expression is associated with increased apoptotic potential. Bax expression was distributed throughout the terminal endbud independent of the observed pattern of apoptosis. A functional role for Bcl-2 family members in regulating endbud apoptosis was demonstrated by the significantly reduced level of apoptosis observed in WAP-Bcl-2 transgenic mice. The pattern of apoptosis and ductal structure of endbuds in these mice was also disrupted. These data demonstrate that p53-independent apoptosis may play a critical role in the early development of the mammary gland.

Author(s):  
Georgia Colleluori ◽  
Jessica Perugini ◽  
Giorgio Barbatelli ◽  
Saverio Cinti

AbstractThe mammary gland (MG) is an exocrine gland present in female mammals responsible for the production and secretion of milk during the process of lactation. It is mainly composed by epithelial cells and adipocytes. Among the features that make the MG unique there are 1) its highly plastic properties displayed during pregnancy, lactation and involution (all steps belonging to the lactation cycle) and 2) its requirement to grow in close association with adipocytes which are absolutely necessary to ensure MG’s proper development at puberty and remodeling during the lactation cycle. Although MG adipocytes play such a critical role for the gland development, most of the studies have focused on its epithelial component only, leaving the role of the neighboring adipocytes largely unexplored. In this review we aim to describe evidences regarding MG’s adipocytes role and properties in physiologic conditions (gland development and lactation cycle), obesity and breast cancer, emphasizing the existing gaps in the literature which deserve further investigation.


1955 ◽  
Vol 46 (2) ◽  
pp. 137-142 ◽  
Author(s):  
E. S. E. Hafez

Thirty-five buffalo heifers were tested daily with fertile males to ascertain the age and live weight at first possible oestrus and conception. Patterns of sexual behaviour were recorded while rectal palpation was carried out to define the conditions of the ovaries and to diagnose pregnancies. The mammary gland development, as well as the intensity of lactation, were noted post partum.1. Pubertal matings were allowed with less certainty than adult matings. The signs of oestrus were intensified by the recurrence of heat and association with the male. Homosexuality was only observed in the first and second oestrus.2. The average age of first oestrus, first conception and first calving were 406, 647 and 963 days respectively. The body weight at first oestrus and first conception were 198 and 319 kg. respectively.3. The number of services/conception ranged from 1 to 7 with an average of 4·25. The number of silent heats/female ranged from 1 to 4 with an average of 1·65. The period elapsing from first oestrus to first conception ranged from 52 to 438 days. Before conception, there was a period of anoestrus which ranged from 115 to 314 days, this was probably due to weak oestrus symptoms.4. The live weights at 28, 84, 140, 196, 252 and 308 days were correlated with the age and live weight at first oestrus as well as the live weight at first conception.5. All the buffalo-cows except two which showed oestrus conceived. Fourteen animals calved normally while fourteen aborted after 131–318 days. The gestation period ranged from 312 to 321 days with an average of 316 days. The birth weight of young ranged from 33 to 40 kg. Seven animals were not lactating while seven gave 1–2 kg. of milk.6. Puberty phenomenon is a gradual phenomenon and is attained in steps: sexual desire, ovulation, oestrus, conception, pregnancy then lactation.


2019 ◽  
Vol 73 ◽  
pp. 909-919
Author(s):  
Ewa Sawicka ◽  
Arkadiusz Woźniak ◽  
Małgorzata Drąg-Zalesińska ◽  
Agnieszka Piwowar

Oncological diseases, due to the still increasing morbidity and mortality, are one of the main problems of modern medicine. Cancer of the mammary gland is the most common cancer among women around the world, and is the second cause of cancer deaths in this group, immediately after lung cancer. This kind of cancer belongs to an estrogen-dependent cancer, with proven associations with hormonal disorders in the body, occurring especially in the perimenopausal period and among women using hormone replacement therapy, as well as a result of the action of various xenobiotics that may interact with the estrogen receptor. Hormone steroids are widely used in medicine and their side effects are constantly discussed. The role of these compounds and their metabolites in maintaining hormonal balance is well understood, while many studies indicate the possible contribution of these steroids in the progression of the cancer process, especially in mammary gland tissue. Therefore, the genotoxic action of this group of compounds is still studied. Due to the limited number of scientific reports, the aim of this paper was to review and critically analyze data from the literature regarding the participation of estrogens (17β-estradiol) and their metabolites (2-methoxy estradiol, 4-hydroxy estradiol, 16α-hydroxyestrone) in the induction of carcinogenesis in mammary gland, in particular concerning the genotoxic activity of 17β-estradiol metabolites.


2009 ◽  
Vol 29 (16) ◽  
pp. 4455-4466 ◽  
Author(s):  
Sarah M. Francis ◽  
Jacqueline Bergsied ◽  
Christian E. Isaac ◽  
Courtney H. Coschi ◽  
Alison L. Martens ◽  
...  

ABSTRACT Transforming growth factor β (TGF-β) is a crucial mediator of breast development, and loss of TGF-β-induced growth arrest is a hallmark of breast cancer. TGF-β has been shown to inhibit cyclin-dependent kinase (CDK) activity, which leads to the accumulation of hypophosphorylated pRB. However, unlike other components of TGF-β cytostatic signaling, pRB is thought to be dispensable for mammary development. Using gene-targeted mice carrying subtle missense changes in pRB (Rb1 ΔL and Rb1NF ), we have discovered that pRB plays a critical role in mammary gland development. In particular, Rb1 mutant female mice have hyperplastic mammary epithelium and defects in nursing due to insensitivity to TGF-β growth inhibition. In contrast with previous studies that highlighted the inhibition of cyclin/CDK activity by TGF-β signaling, our experiments revealed that active transcriptional repression of E2F target genes by pRB downstream of CDKs is also a key component of TGF-β cytostatic signaling. Taken together, our work demonstrates a unique functional connection between pRB and TGF-β in growth control and mammary gland development.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Gloria Ocran ◽  
Livingstone Divine Caesar

PurposeDespite the introduction of structural reforms to the students' loan scheme (SLS) in Ghana's higher education sector, patronage is still low. This paper aims to examine the complexity of technological and behavioural factors underpinning the low rate of students' loan adoption in Ghana. It further contributes to the body of knowledge by exploring the moderating role of financial knowledge in the hypothesized relationships.Design/methodology/approachUsing a positivistic research approach, a sample of 700 tertiary students with experience in accessing SLSs were surveyed. An 88% response rate was realized and the data analysed using descriptive statistics, exploratory and confirmatory factor analysis.FindingsFour dimensions of technological factors (relative advantage, trialability, observability and compatibility) and two of behavioural factors (attitude and control behaviour) were positively related to adoption of the SLS. Financial knowledge only moderated the relationship between compatibility, attitude, behavioural control and students' loan adoption.Practical implicationsFinancial knowledge plays a critical role in influencing the investment decisions of people. Management of SLSs needs to offer financial education to targeted parents/students to clear misconceptions. It is also imperative that all other technical challenges are addressed to enhance adoption rates for the SLS. Review of guarantor requirements is needed also.Originality/valueThis paper introduces financial knowledge as a moderating variable to investigate the hypothesized relationships. It offers a developing country insight into how technological/behavioural factors and financial knowledge might be impacting adoption of SLSs.


Author(s):  
W. Mark Saltzman

Perhaps the simplest realization of tissue engineering involves the direct administration of a suspension of engineered cells—cells that have been isolated, characterized, manipulated, and amplified outside of the body. One can imagine engineering diverse and useful properties into the injected cells: functional enzymes, secretion of drugs, resistance to immune recognition, and growth control. We are most familiar with methods for manipulating the cell internal chemistry by introduction or removal of genes; for example, the first gene therapy experiments involved cells that were engineered to produce a deficient enzyme, adenine deaminase (see Chapter 2). But genes also encode systems that enable cell movement, cell mechanics, and cell adhesion. Conceivably, these systems can be modified to direct the interactions of an administered cell with its new host. For example, cell adhesion signals could be introduced to provide tissue targeting, cytoskeleton-associated proteins could be added to alter viscosity and deformability (in order to prolong circulation time), and motor proteins could be added to facilitate cell migration. Ideally, cell fate would also be engineered, so that the cell would move to the appropriate location in the body, no matter how it was administered; for example, transfused liver cells would circulate in the blood and, eventually, crawl into the liver parenchyma. Cells find their place in developing organisms by a variety of chemotactic and adhesive signals, but can these same signaling mechanisms be engaged to target cells administered to an adult organism? We have already considered the critical role of cell movement in development in Chapter 3. In this chapter, the utility of cell trafficking in tissue engineering is approached by first considering the normal role of cell recirculation and trafficking within the adult organism. Most cells can be easily introduced into the body by intravenous injection or infusion. This procedure is particularly appropriate for cells that function within the circulation; for example, red blood cells (RBCs) and lymphocytes. The first blood transfusions into humans were performed by Jean-Baptiste Denis, a French physician, in 1667. This early appearance of transfusion is startling, since the circulatory system was described by William Harvey only a few decades earlier, in 1628.


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