Notch signaling has been widely demonstrated to be responsible for cell fate determination during normal development and implicated in human T-cell leukemia and mouse mammary carcinomas. Here we show ...that Notch signaling may be involved in prostatic development and cancer cell growth. In situ hybridization and reverse transcription-PCR analyses revealed that Notch1 was expressed in prostate epithelial cells during normal development and in prostate cancer cells. Characterization of Notch1-green fluorescent protein transgenic mice, in which the expression of reporter green fluorescent protein is under the control of the Notch1 promoter, indicated that Notch1-expressing cells were associated with the basal epithelial cell population in the prostate. Examination of the transgenic adenocarcinoma of the mouse prostate showed that expression of Notch1 was elevated in malignant prostatic epithelial cells of primary and metastatic tumors. Expression of Notch ligands, however, was low or undetectable in cultured prostate cancer cells or in malignant prostatic epithelial cells in transgenic adenocarcinoma of the mouse prostate. Furthermore, overexpression of a constitutively active form of Notch1 inhibited the proliferation of various prostate cancer cells, including DU145, LNCaP, and PC3 cells. Taken together, our data indicate for the first time that Notch signaling may play a role in murine prostatic development and tumorigenesis.
Gamma-ray flash generation in near critical density (NCD) target irradiated by four symmetrical colliding laser pulses is numerically investigated. With peak intensities about \(10^{23}\) W/cm\(^2\), ...the laser pulses boost electron energy through direct laser acceleration, while pushing them inward with the ponderomotive force. After backscattering with counter-propagating laser, the accelerated electron is trapped in the optical lattice or the electromagnetic standing waves (SW) created by the coherent overlapping of the laser pulses, and emits gamma-ray photons in Multiple Compton Scattering regime, where electrons act as a medium transferring energy from the laser to gamma-rays. The energy conversion rate from laser pulses to gamma-ray can be as high as 50\%
Initial geometrical distribution and fluctuation can affect the collective expansion in relativistic heavy-ion collisions. This effect may be more evident in small system (such as B + B) than in ...large one (Pb + Pb). This work presents the collision system dependence of collective flows and discusses about effects on collective flows from initial fluctuations in a framework of a multiphase transport model. The results shed light on system scan on experimental efforts to small system physics.
Although hair cells regenerate spontaneously in birds and lower vertebrates following injury, there is yet no effective way to stimulate hair cell regeneration in mature mammalian inner ears. Here we ...report that a large number of hair cells are produced in the sensory epithelium of cultured adult rat utricular maculae, via adenovirus-mediated overexpression of
Hath1, a human
atonal homolog. The generation of new hair cells via
Hath1 expression does not involve cell proliferation based on bromodeoxyuridine immunocytochemistry. Furthermore, using a similar approach, hair cells are regenerated following aminoglycoside injury in these cultures. These data show conclusively that mature mammalian inner ears have the competence to produce a large number of new hair cells. Local adenoviral gene therapy in the inner ear may be a potential approach to treatment of hearing and balance disorders.
Notch expression is frequently associated with progenitor cells, and its function is crucial for development. Our recent work
showing that Notch1 is selectively expressed in basal epithelial cells of ...the prostate and higher Notch1 expression during
development suggests that Notch1-expressing cells may define progenitor cells in the prostate. To test this hypothesis, we
have generated a transgenic mouse line in which the Notch1-expressing cells can be ablated in a controlled manner. Specific
targeting was achieved by expressing the bacterial nitroreductase, an enzyme that catalyzes its substrate into a cytotoxin
capable of inducing apoptosis, under the Notch1 promoter. Cell death in transgenic prostate was confirmed by histological analyses including terminal dUTP nick-end labeling
and caspase 3 immunocytochemical staining. We evaluated the consequences of ablation of Notch1-expressing cells in two systems,
organ culture of early postnatal prostates and re-growth of prostate in castrated mice triggered by hormone replacement. Our
data show that elimination of Notch1-expressing cells inhibited the branching morphogenesis, growth, and differentiation of
early postnatal prostate in culture and impaired prostate re-growth triggered by hormone replacement in castrated mice. Furthermore,
we found that Notch1 expression following castration and hormone replacement was concomitant with known basal cell markers
p63 and cytokeratin 14 and was high in the proliferative human prostate epithelial cells. Taken together, these data suggest
that Notch1-expressing cells define the progenitor cells in the prostatic epithelial cell lineage, which are indispensable
for prostatic development and re-growth.
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