DNA synthesis in the stromal cells of mouse mammary gland tumors

1971 ◽  
Vol 72 (1) ◽  
pp. 798-800
Author(s):  
N. N. Belyaeva ◽  
Yu. M. Vasil'ev
1984 ◽  
Vol 28 (2) ◽  
pp. 179-185 ◽  
Author(s):  
Lech Zwierzchowski ◽  
Danuta Kleczkowska ◽  
Wieslaw Niedbalski ◽  
Izabela Grochowska

1980 ◽  
Vol 214 (2) ◽  
pp. 215-218 ◽  
Author(s):  
David W. Borst ◽  
William B. Mahoney

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3694-3703 ◽  
Author(s):  
Aino Kuorelahti ◽  
Susana Rulli ◽  
Ilpo Huhtaniemi ◽  
Matti Poutanen

Transgenic (TG) mice expressing human chorionic gonadotropin (hCG) β-subunit under the ubiquitin C promoter, presenting with a moderately elevated level of LH/hCG bioactivity develop multiple neoplasms secondary to the endocrine abnormalities, including mammary gland tumors after the age of 9 months. The increased levels of circulating estradiol, progesterone, and prolactin of the TG females after puberty boost the lobuloalveolar development in the mammary gland resulting ultimately in the formation of estrogen and progesterone receptor-negative, malignant tumors. These tumors have a similar histopathology with those observed in TG mice with activated wnt/β-catenin pathway, showing increased expression of β-catenin, also a common finding in human breast tumors. Transdifferentiation is observed in mammary tumors of the hCGβ TG mice, accompanied by abnormal expression of the Wnt genes in the tumorous and nontumorous mammary gland tissue. Specifically we found increased expression of Wnt5b in the TG mammary glands at the age of 3 months and up-regulation of Wnt7b and -5b in the subsequently appearing tumors. Importantly, hCG was found to up-regulate these wnt ligands in mouse mammary gland, independent of the changes in ovarian steroidogenesis. Thus, the hCGβ-overexpressing TG mice represent a novel model that links enhanced hCG action to dysregulated wnt signaling in the mammary gland, resulting in β-catenin-stabilizing mammary tumorigenesis. The novel finding of hCG up-regulating wnt7b and wnt5b could contribute to pregnancy-induced breast cancer in humans.


1982 ◽  
Vol 53 (1) ◽  
pp. 97-114 ◽  
Author(s):  
B.K. Vonderhaar ◽  
G.H. Smith

Epithelial cells in mammary gland explants from mice assume a secretory appearance and synthesize the milk proteins, casein and alpha-lactalbumin, when cultured in the presence of insulin, hydrocortisone and prolactin. In cells from the glands of mature virgin animals such syntheses are known to require DNA synthesis. Addition of cytosine-beta-D-arabinofuranoside to the explant cultures suppresses both hormonally induced DNA synthesis and enhanced production of milk protein. To determine the level at which this block in terminal differentiation occurs, epithelial cell pellets were prepared from virgin mouse mammary gland explants cultured with various combination of insulin, hydrocortisone and prolactin, and subsequently examined by light and electron microscopy. We observed that the epithelial cells cultured in the presence of all three hormones developed fully, cytologically and ultrastructurally, even in the absence of DNA synthesis in vitro. Likewise, these cells were able to incorporate [3H]uridine into RNA efficiently and to incorporate amino acids into acid-precipitable polypeptides at levels equivalent to the untreated controls. However, immunoprecipitation of newly synthesized casein peptides showed that no new synthesis of casein occurred in cells prevented from synthesizing DNA. These data show uncoupling of cytological development and synthesis of milk protein in mammary explants from mature virgin mice inhibited from synthesizing DNA.


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