Cell proliferation is not required for the initiation of early cleft formation in mouse embryonic submandibular epithelium in vitro

Development ◽  
1987 ◽  
Vol 99 (3) ◽  
pp. 429-437 ◽  
Author(s):  
Y. Nakanishi ◽  
T. Morita ◽  
H. Nogawa
Keyword(s):  
Cell Proliferation ◽  
Dna Synthesis ◽  
Specific Inhibitor ◽  
X Rays ◽  
X Ray ◽  
Mitotic Figures ◽  
Cleft Formation ◽  
Proliferation In Vitro

An X-ray irradiation method was employed to analyse the role of cell proliferation in vitro in the cleft formation of mouse embryonic submandibular epithelium at early stages. When the mid 12-day gland was exposed to 200 rad of X-rays, the growth was severely retarded. In contrast, late 12-day and early 13-day glands grew apparently in a normal fashion, as did the control gland, for up to 40 h. In either case, they formed shallow clefts within 10 h of culture. With 1000 rad irradiation, the mid 12-day gland did not grow at all, but formed clefts within 20 h of culture followed by a rapid degeneration. Under the same conditions, the growth of the late 12-day gland, which was at the stage just before branching, was retarded until 10 h of culture, followed by a slight increase in epithelial size, but cleft formation was also observed within 6–10 h, as in the control gland. When exposed to a dose of 1000 rad of X-rays, the early 13-day and the late 12-day glands exhibited similar radiosensitivity; the initial narrow clefts in the epithelium deepened and new clefts began to form within 6–10 h of culture. [3H]thymidine incorporation studies revealed that a dose of 1000 rad reduced DNA synthesis of mid and late 12-day glands by 72 and 65%, respectively. Histological examination of X-irradiated late 12-day gland showed that mitotic figures were rarely seen in the epithelium at 6 h of culture. Aphidicolin, a specific inhibitor of DNA synthesis, could not halt the cleft formation of the late 12-day gland. In this experiment 89% of DNA synthesis was inhibited. Treatment of an X-ray irradiated late 12-day gland with aphidicolin blocked 92% of the DNA synthesis, but did not prevent cleft formation taking place. These results indicate that neither cell division nor DNA synthesis, is required for the initiation process of the cleft formation of the mouse embryonic submandibular epithelium at early morphogenetic stages in vitro.

ROLE OF PAF AND OXIDANT AGENTS ON VASCULAR CELL PROLIFERATION. IN VITRO IMPLICATION OF MTOR-DEPENDENT PATHWAY.

2004 ◽  
Vol 78 ◽  
pp. 741-742
Author(s):  
I Rama ◽  
M Riera ◽  
J Torras ◽  
J M Cruzado ◽  
I Herrero-Fresneda ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Vascular Cell ◽  
Proliferation In Vitro ◽  
Dependent Pathway

scholarly journals HNRNPA2B1 promotes multiple myeloma progression by increasing AKT3 expression via m6A-dependent stabilization of ILF3 mRNA

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fengjie Jiang ◽  
Xiaozhu Tang ◽  
Chao Tang ◽  
Zhen Hua ◽  
Mengying Ke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Aberrant Expression ◽  
The Stability ◽  
Induced Apoptosis ◽  
Proliferation In Vitro

AbstractN6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic RNAs while accumulating studies suggest that m6A aberrant expression plays an important role in cancer. HNRNPA2B1 is a m6A reader which binds to nascent RNA and thus affects a perplexing array of RNA metabolism exquisitely. Despite unveiled facets that HNRNPA2B1 is deregulated in several tumors and facilitates tumor growth, a clear role of HNRNPA2B1 in multiple myeloma (MM) remains elusive. Herein, we analyzed the function and the regulatory mechanism of HNRNPA2B1 in MM. We found that HNRNPA2B1 was elevated in MM patients and negatively correlated with favorable prognosis. The depletion of HNRNPA2B1 in MM cells inhibited cell proliferation and induced apoptosis. On the contrary, the overexpression of HNRNPA2B1 promoted cell proliferation in vitro and in vivo. Mechanistic studies revealed that HNRNPA2B1 recognized the m6A sites of ILF3 and enhanced the stability of ILF3 mRNA transcripts, while AKT3 downregulation by siRNA abrogated the cellular proliferation induced by HNRNPA2B1 overexpression. Additionally, the expression of HNRNPA2B1, ILF3 and AKT3 was positively associated with each other in MM tissues tested by immunohistochemistry. In summary, our study highlights that HNRNPA2B1 potentially acts as a therapeutic target of MM through regulating AKT3 expression mediated by ILF3-dependent pattern.

scholarly journals Exploiting GRK2 Inhibition as a Therapeutic Option in Experimental Cancer Treatment: Role of p53-Induced Mitochondrial Apoptosis

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3530
Author(s):  
Jessica Gambardella ◽  
Antonella Fiordelisi ◽  
Gaetano Santulli ◽  
Michele Ciccarelli ◽  
Federica Andrea Cerasuolo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Nude Mice ◽  
Specific Inhibitor ◽  
Cancer Cell Proliferation ◽  
In Vivo Models ◽  
P53 Expression

The involvement of GRK2 in cancer cell proliferation and its counter-regulation of p53 have been suggested in breast cancer even if the underlying mechanism has not yet been elucidated. Furthermore, the possibility to pharmacologically inhibit GRK2 to delay cancer cell proliferation has never been explored. We investigated this possibility by setting up a study that combined in vitro and in vivo models to underpin the crosstalk between GRK2 and p53. To reach this aim, we took advantage of the different expression of p53 in cell lines of thyroid cancer (BHT 101 expressing p53 and FRO cells, which are p53-null) in which we overexpressed or silenced GRK2. The pharmacological inhibition of GRK2 was achieved using the specific inhibitor KRX-C7. The in vivo study was performed in Balb/c nude mice, where we treated BHT-101 or FRO-derived tumors with KRX-C7. In our in vitro model, FRO cells were unaffected by GRK2 expression levels, whereas BHT-101 cells were sensitive, thus suggesting a role for p53. The regulation of p53 by GRK2 is due to phosphorylative events in Thr-55, which induce the degradation of p53. In BHT-101 cells, the pharmacologic inhibition of GRK2 by KRX-C7 increased p53 levels and activated apoptosis through the mitochondrial release of cytochrome c. These KRX-C7-mediated events were also confirmed in cancer allograft models in nude mice. In conclusion, our data showed that GRK2 counter-regulates p53 expression in cancer cells through a kinase-dependent activity. Our results further corroborate the anti-proliferative role of GRK2 inhibitors in p53-sensitive tumors and propose GRK2 as a therapeutic target in selected cancers.

Inhibition of pig granulosa cell adhesion and growth in vitro by immunoneutralization of epithelial cadherin

Reproduction ◽  
2000 ◽  
pp. 275-281 ◽  
Author(s):  
KM Kirkup ◽  
AM Mallin ◽  
CA Bagnell
Keyword(s):  
Cell Proliferation ◽  
Cell Adhesion ◽  
Dna Synthesis ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Cell Contact ◽  
Mouse Ascites ◽  
Proliferation In Vitro ◽  
E Cadherin

Epithelial cadherin (E-cadherin) is a member of the cadherin family of calcium-dependent cell adhesion molecules and is present in the ovary. Although expression of E-cadherin is high in healthy pig granulosa cells and low in granulosa cells of atretic follicles, the importance of E-cadherin-mediated adhesion in granulosa cell function is unclear. The aim of the present study was to determine the impact of immunoneutralization of E-cadherin on granulosa cell adhesion, DNA synthesis and cell proliferation in vitro. Before attachment, pig granulosa cells were exposed to a monoclonal E-cadherin antibody (DECMA-1) which blocks E-cadherin function. Controls included substitution of the antibody with either mouse ascites fluid or another E-cadherin antibody directed against the cytoplasmic domain and which was therefore inaccessible in intact cells. Both granulosa cell proliferation and insulin-like growth factor I-induced DNA synthesis were inhibited significantly in the presence of DECMA-1 compared with controls (P < 0.05). Control granulosa cells in culture formed large clusters with many cells packed tightly together. However, after 48 h exposure to the function-perturbing E-cadherin antibody, there was a significant decrease in the size of the granulosa cell clusters (P < 0.05) and the degree of cell-cell contact was reduced compared with control cultures. No effects on DNA synthesis, cell proliferation or cell adhesion were observed when DECMA-1 was substituted with either mouse ascites fluid or the antibody specific for the cytoplasmic domain of E-cadherin. In conclusion, these data provide evidence to support the hypothesis that E-cadherin is important for maintaining granulosa cell contact, DNA synthesis and cell proliferation in vitro. These results indicate that E-cadherin plays a fundamental role in maintaining both the structure and function of ovarian follicles.

Regulation of rat alveolar type 2 cell proliferation in vitro involves type II cAMP-dependent protein kinase

2007 ◽  
Vol 292 (1) ◽  
pp. L232-L239 ◽  
Author(s):  
Jan T. Samuelsen ◽  
Per E. Schwarze ◽  
Henrik S. Huitfeldt ◽  
E. Vibeke Thrane ◽  
Marit Låg ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Alveolar Type ◽  
Regulatory Subunits ◽  
Anchoring Protein ◽  
Dependent Protein ◽  
Cycle Dependent ◽  
Proliferation In Vitro

To elucidate the role of cAMP and different cAMP-dependent protein kinases (PKA; A-kinase) in lung cell proliferation, we investigated rat alveolar type 2 cell proliferation in relation to activation or inhibition of PKA and PKA regulatory subunits (RIIα and RIα). Both the number of proliferating type 2 cells and the level of different regulatory subunits varied during 7 days of culture. The cells exhibited a distinct peak of proliferation after 5 days of culture. This proliferation peak was preceded by a rise in RIIα protein level. In contrast, an inverse relationship between RIα and type 2 cell proliferation was noted. Activation of PKA increased type 2 cell proliferation if given at peak RIIα expression. Furthermore, PKA inhibitors lowered the rate of proliferation only when a high RII level was observed. An antibody against the anchoring region of RIIα showed cell cycle-dependent binding in contrast to antibodies against other regions, possibly related to altered binding to A-kinase anchoring protein. Following activation of PKA, relocalization of RIIα was confirmed by immunocytochemistry. In conclusion, it appears that activation of PKA II is important in regulation of alveolar type 2 cell proliferation.

scholarly journals MiR-155-5p suppresses SOX1 to promote proliferation of cholangiocarcinoma via RAF/MEK/ERK pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Da Wang ◽  
Fei Xiong ◽  
Guanhua Wu ◽  
Wenzheng Liu ◽  
Bing Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Close Relation ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Erk Phosphorylation ◽  
Overexpressing Cell ◽  
Proliferation In Vitro

Abstract Background Accumulating evidence has demonstrated the close relation of SOX1 with tumorigenesis and tumor progression. Upregulation of SOX1 was recently shown to suppress growth of human cancers. However, the expression and role of SOX1 in cholangiocarcinoma (CCA) is not well characterized. Methods Expression levels of SOX1 in CCA tissues and normal bile duct tissues were examined using public GEO database. Western blot and immunohistochemistry were used to confirm the expression levels. Cell proliferation assay (CCK-8) and colony formation assay were performed to assess proliferation of CCA cells. A mouse model of subcutaneous transplantable tumors was used to evaluated proliferation of CCA in vivo. The putative regulating factor of SOX1 were determined using Targetscan and dual-luciferase reporter assay. Results SOX1 was downregulated in CCA tissues. Overexpression of SOX1 significantly inhibited cell proliferation in vitro and suppressed tumor growth in vivo. miR-155-5p directly targeted the 3′-untranslated region (3′UTR) of SOX1 and inhibited expression of SOX1, resulting in the activation of RAF, MEK and ERK phosphorylation, and thus CCA proliferation. However, restoration of SOX1 expression in miR-155-5p overexpressing cell lines decreased the phosphorylation level of RAF, MEK and ERK, as well as the proliferation of CCA cells. Conclusion MiR-155-5p decreased the expression of SOX1 by binding to its 3′UTR, which activated the RAF/MEK/ERK signaling pathway and promoted CCA progression.

scholarly journals MiR-155-5p Suppress SOX1 to Promote the Proliferation of Cholangiocarcinoma via RAF/MEK/ERK Pathway

2021 ◽  
Author(s):  
Da Wang ◽  
Fei Xiong ◽  
Guanhua Wu ◽  
Wenzheng Liu ◽  
Bing Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Luciferase Reporter ◽  
Phosphorylation Level ◽  
Erk Phosphorylation ◽  
Overexpressing Cell ◽  
Proliferation In Vitro ◽  
Geo Database

Abstract BackgroundAccumulating evidences indicate that SOX1 is closely related to tumorigenesis and development, upregulation of SOX1 is recently reported to suppress growth of human cancers. However, the expression and role of SOX1 in cholangiocarcinoma (CCA) remain unknown.MethodsThe expression levels of SOX1 in CCA tissues and normal bile duct tissues were examined by public GEO database, and western blot and immunohistochemistry were used to confirm the expression again. Cell proliferation assay (CCK-8) and colony formation assay were performed to determine proliferation of CCA cells. A model of transplatable subcutaneously tumors in mouse was used to evaluated proliferation of CCA in vivo. The putative regulating factor of SOX1 were disclosed by Targetscan and a dual-luciferase reporter assay.ResultsSOX1 was downregulated in CCA tissues. Overexpression of SOX1 significantly inhibited cell proliferation in vitro and tumor growth in vivo. Furthermore, miR-155-5p directly targets 3’UTR of SOX1 and inhibits expression of SOX1, resulting in the activation of RAF, MEK and ERK phosphorylation and thus CCA proliferation. However, when SOX1 expression was restored in miR-155-5p overexpressing cell lines, the phosphorylation level of RAF, MEK and ERK were decreased, as well as the proliferation of CCA cells.ConclusionMiR-155-5p could bind to the 3’UTR of SOX1 to decrease the expression of SOX1, and further activated the RAF/MEK/ERK signaling pathway to promote CCA progression.

scholarly journals Cullin-1 Regulates MG63 Cell Proliferation and Metastasis and is a Novel Prognostic Marker of Osteosarcoma

2017 ◽  
Vol 32 (2) ◽  
pp. 202-209 ◽  
Author(s):  
Qinghua Cheng ◽  
Guoyong Yin
Keyword(s):  
Cell Proliferation ◽  
Mg63 Cell ◽  
Osteosarcoma Cell ◽  
Mmp9 Expression ◽  
Proliferation And Metastasis ◽  
Reliable Marker ◽  
Proliferation In Vitro

Background There is no reliable marker available for early detection, diagnostic confirmation or disease prognosis of osteosarcoma. Cullin-1 (CUL1) is a newly reported tumor-related gene, and we aimed to unravel its role in osteosarcoma. Methods We used immunohistochemistry to analyze the correlation between CUL1 expression and clinicopathological variables and patient survival. To evaluate the function of CUL1, a group of 28 osteosarcoma patients were recruited for this study. The role of regulation of CUL1 in osteosarcoma was studied in vitro and in vivo. In addition, we further investigated the signaling pathway of CUL1 in osteosarcoma progression. Results We first discovered that CUL1 expression was up-regulated in human osteosarcoma tissues and inversely correlated with osteosarcoma differentiation. In addition, CUL1 promotes osteosarcoma cell proliferation in vitro and in vivo. We also found that CUL1 promotes osteosarcoma cell invasion and metastasis in vitro and in vivo. High levels of CUL1 promote osteosarcoma progression via up-regulation of MMP9 expression. Conclusions Our results demonstrate that increased CUL1 expression is significantly correlated with poor prognosis of patients with osteosarcoma. CUL1 might be an important marker and a therapeutic target for osteosarcoma.

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