scholarly journals MMTV promoter-regulated caveolin-1 overexpression yields defective parenchymal epithelia in multiple exocrine organs of transgenic mice

2010 ◽  
Vol 89 (1) ◽  
pp. 9-19 ◽  
Author(s):  
Guang Yang ◽  
Sanghee Park ◽  
Guangwen Cao ◽  
Alexei Goltsov ◽  
Chengzhen Ren ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Caveolin 1 ◽  
Mmtv Promoter

scholarly journals Loss of Caveolin-1 Gene Expression Accelerates the Development of Dysplastic Mammary Lesions in Tumor-Prone Transgenic Mice

2003 ◽  
Vol 14 (3) ◽  
pp. 1027-1042 ◽  
Author(s):  
Terence M. Williams ◽  
Michelle W.-C. Cheung ◽  
David S. Park ◽  
Babak Razani ◽  
Alex W. Cohen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Suppressor ◽  
Transgenic Mice ◽  
Histological Grade ◽  
Dominant Negative ◽  
Breast Cancers ◽  
Suppressor Activity ◽  
Caveolin 1 ◽  
Dominant Negative Mutation

Caveolin-1 is the principal structural component of caveolae microdomains, which represent a subcompartment of the plasma membrane. Several independent lines of evidence support the notion that caveolin-1 functions as a suppressor of cell transformation. For example, the human CAV-1 gene maps to a suspected tumor suppressor locus (D7S522/7q31.1) that is frequently deleted in a number of carcinomas, including breast cancers. In addition, up to 16% of human breast cancers harbor a dominant-negative mutation, P132L, in the CAV-1 gene. Despite these genetic associations, the tumor suppressor role of caveolin-1 still remains controversial. To directly assess the in vivo transformation suppressor activity of the caveolin-1 gene, we interbred Cav-1 (−/−) null mice with tumor-prone transgenic mice (MMTV-PyMT) that normally develop multifocal dysplastic lesions throughout the entire mammary tree. Herein, we show that loss of caveolin-1 gene expression dramatically accelerates the development of these multifocal dysplastic mammary lesions. At 3 wk of age, loss of caveolin-1 resulted in an approximately twofold increase in the number of lesions (foci per gland; 3.3 ± 1.0 vs. 7.0 ± 1.2) and an approximately five- to sixfold increase in the total area occupied by these lesions. Similar results were obtained at 4 wk of age. However, complete loss of caveolin-1 was required to accelerate the appearance of these dysplastic mammary lesions, because Cav-1 (+/−) heterozygous mice did not show any increases in foci development. We also show that loss of caveolin-1 increases the extent and the histological grade of these mammary lesions and facilitates the development of papillary projections in the mammary ducts. Finally, we demonstrate that cyclin D1 expression levels are dramatically elevated in Cav-1 (−/−) null mammary lesions, consistent with the accelerated appearance and growth of these dysplastic foci. This is the first in vivo demonstration that caveolin-1 can function as a transformation suppressor gene.

scholarly journals MMTV promoter hypomethylation is linked to spontaneous and MNU associated c-neu expression and mammary carcinogenesis in MMTV c-neu transgenic mice

Oncogene ◽  
2001 ◽  
Vol 20 (42) ◽  
pp. 6009-6017 ◽  
Author(s):  
Hang Zhou ◽  
Wei-dong Chen ◽  
Xiusheng Qin ◽  
Keunmyoung Lee ◽  
Lili Liu ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Mammary Carcinogenesis ◽  
Mmtv Promoter

Curcumin Decreases Hyperphosphorylation of Tau by Down-Regulating Caveolin-1/GSK-3β in N2a/APP695swe Cells and APP/PS1 Double Transgenic Alzheimer’s Disease Mice

2017 ◽  
Vol 45 (08) ◽  
pp. 1667-1682 ◽  
Author(s):  
Jieyun Sun ◽  
Xiong Zhang ◽  
Chen Wang ◽  
Zhipeng Teng ◽  
Yu Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Amyloid Peptide ◽  
Phosphorylated Tau ◽  
Curcumin Treatment ◽  
Protein Precursor ◽  
Caveolin 1 ◽  
Gsk 3Β ◽  
Cholesterol Regulation

Caveolin-1, the marker protein of membranal caveolae, is not only involved in cholesterol regulation, but also participates in the cleavage of amyloid [Formula: see text]-protein precursor (APP) and the generation of [Formula: see text]-amyloid peptide. It has been reported to be tightly related with Tau. In our previous studies, curcumin has been confirmed to play a neuroprotective role in Alzheimer’s disease (AD), but its effects on Caveolin-1, Tau and their correlation, and the mechanism is still unknown. As such, in the present study, N2a/WT cells, N2a/APP695swe cell and six-month-old APP/PS1 double transgenic mice were enrolled. After curcumin treatment, the expression of Caveolin-1, Tau and their relationship was detected, and the potential mechanisms were explored. The results showed that in the N2a/APP695swe cells, curcumin not only decreased the number of caveolae, but also made their membrane to be thinner; and curcumin could decreased the expression of phosphorylated Tau (P-Tau(ser404)/Tau) and Caveolin-1 ([Formula: see text]), but the expression of phosphorylated GSK-3[Formula: see text] (P-GSK-3[Formula: see text]/GSK-3[Formula: see text] was increased ([Formula: see text]). In APP/PS1 transgenic mice, the same results were observed. Taken together, our data suggest that curcumin may play an important role in AD via reducing Caveolin-1, inactivating GSK-3[Formula: see text] and inhibiting the abnormal excessive phosphorylation of Tau, which will provide a new theory for AD treatment with curcumin.

Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

1996 ◽  
Vol 54 ◽  
pp. 14-15
Author(s):  
C. G. Plopper ◽  
C. Helton ◽  
A. J. Weir ◽  
J. A. Whitsett ◽  
T. R. Korfhagen
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Transgenic Mice ◽  
Blood Vessels ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Alveolar Air ◽  
Parenchymal Tissue ◽  
Air Space ◽  
Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

1422: Oxytocin Receptor and Caveolin-1 Expression in the Prostate of Young and Aging Male

2005 ◽  
Vol 173 (4S) ◽  
pp. 385-386
Author(s):  
Gregor Bötticher ◽  
Zsófia Herbert ◽  
Erdogan Sendemir ◽  
Andreas Aschoff ◽  
Gustav Friedrich Jirikowski ◽  
...  
Keyword(s):  
Oxytocin Receptor ◽  
Aging Male ◽  
Caveolin 1
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