• Toxicological Research
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• v.23 no.3
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• pp.197-205
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• 2007

Cancer metastasis is a major determinant of cancer patient mortality. Mounting evidence favors a strong positive role for $TGF-{\beta}$ in human cancer progression. The complex pattern on cross-talk of $TGF-{\beta}$ and the related other signaling pathways is an important area of investigation that will ultimately contribute to understanding of the bifunctional role of $TGF-{\beta}$ in cancer progression. This review summarizes some of the current understanding of $TGF-{\beta}$ signaling with a major focus in its contribution to the tumor cell invasion and metastasis. Five issues are addressed in this review: (1) $TGF-{\beta}$ signaling, (2) $TGF-{\beta}$ and EMT, (3) $TGF-{\beta}$ and MMP, (4) $TGF-{\beta}$ and Ras, and (5) Role of $TGF-{\beta}$ in invasion and metastasis. Due to the bifunctional cellular effects of $TGF-{\beta}$, as a tumor promoter and a tumor suppressor, more precisely defined $TGF-{\beta}$ signaling pathways need to be elucidated. According to the current literature, $TGF-{\beta}$ is clearly a major factor stimulating tumor progression through a complex spectrum of the interplay and cross-talk between various signaling molecules. Understanding the role of $TGF-{\beta}$ in invasion and metastasis will provide valuable information on establishing strategies to manipulate $TGF-{\beta}$ signaling which should be a high priority for the development of anti-metastatic therapeutics.

• Proceedings of the Korean Society of Sericultural Science Conference
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• 2003.10a
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• pp.145-146
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• 2003

Overproduction of transforming growth factor (TGF)-$\beta$l has been implicated in the pathogenesis of fibrotic diseases. TGF-$\beta$l plays a crucial role in the accumulation of extracellular matrix (ECM) in human and experimental glomerular diseases. However, it remains unclear whether inhibition of TGF- $\beta$l overproduction would suppress TGF- $\beta$l induced ECM accumulation. To inhibit the overproduction of TGF- $\beta$l in experimental glomerulonephritis induced by anti-Thy 1.1 antibody, we introduced antisense oligodeoxynucleotides (ODN) fur TGF- $\beta$l into the nephritic kidney by the HVJ-liposome-mediated gene transfer method. (omitted)

• Clinical and Experimental Reproductive Medicine
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• v.48 no.2
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• pp.124-131
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• 2021

Objective: Approximately 30% of preeclamptic pregnancies exhibit abnormal liver function tests. We assessed liver injury-associated enzyme levels and circulating transforming growth factor beta (TGF-β) levels in an arginine vasopressin (AVP)-induced pregnant Sprague-Dawley rat model. Methods: Pregnant and non-pregnant Sprague-Dawley rats (n=24) received AVP (150 ng/hr) subcutaneously via mini-osmotic pumps for 18 days. Blood pressure was measured, urine samples were collected, and all animals were euthanized via isoflurane. Blood was collected to measure circulating levels of TGF-β1-3 isomers and liver injury enzymes in pregnant AVP (PAVP), pregnant saline (PS), non-pregnant AVP (NAVP), and non-pregnant saline (NS) rats. Results: The PAVP group showed significantly higher systolic and diastolic blood pressure than both saline-treated groups. The weight per pup was significantly lower in the AVP-treated group than in the saline group (p<0.05). Circulating TGF-β1-3 isomer levels were significantly higher in the PAVP rats than in the NS rats. However, similar TGF-β1 and TGF-β3 levels were noted in the PS and PAVP rats, while TGF-β2 levels were significantly higher in the PAVP rats. Circulating liver-type arginase-1 and 5'-nucleotidase levels were higher in the PAVP rats than in the saline group. Conclusion: This is the first study to demonstrate higher levels of TGF-β2, arginase, and 5'-nucleotidase activity in PAVP than in PS rats. AVP may cause vasoconstriction and increase peripheral resistance and blood pressure, thereby elevating TGF-β and inducing the preeclampsia-associated inflammatory response. Future studies should explore the mechanisms through which AVP dysregulates liver injury enzymes and TGF-β in pregnant rats.

• Biomedical Science Letters
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• v.11 no.2
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• pp.175-183
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• 2005

The two major isoflavones in soy, genistein and daidzein, are well known to prevent hormone-dependent cancers by their anti estrogenic activity. The exact molecular mechanisms for the protective action are, however, not provided yet. It has been reported that genistein and daidzein have a potential anticancer activity through their antiproliferative effect in many hormone-dependent cancer cell lines. Transforming growth $factor-\beta1(TGF-\beta1)$ has also been found to have cell growth inhibitory effect, especially in mammary epithelial cells. This knowledge led to a hypothetical mechanism that the soy isoflavones-induced growth inhibitory effect can be derived from the regulation of $TGF-\beta1$ and $TGF-\beta$ receptors. In order to test this hypothesis, the effects of the soy isoflavones at various concentrations and periods on the expression of $TGF-\beta1$and $TGF-\beta$ receptors were investigated by using Northern blot analysis in human breast carcinoma epithelial cell lines, an estrogen receptor positive cell line (MCF-7) and an estrogen receptor negative cell line (MDA-MB-231). As a result, only genistein has shown a profound dose-dependent effect on $TGF-\beta1$ expression in the $ER^+$ cell line within the range of doses tested, and the expression levels are correspondent to their inhibitory activities of cell growth. Moreover, daidzein showed down-regulated $TGF-\beta1$ expression at a low dose, the cell growth proliferation was promoted at the same condition. Therefore, antiproliferative activity of the soy isoflavones can be mediated by $TGF-\beta1$ expression, and the effects are mainly, if not all, occurred by ER dependent pathway. The expression of $TGF-\beta$ receptors was induced at a lower dose than the one for $TGF-{\beta}1$ induction regardless of the presence of ER, and the expression patterns are similar to those of the cell growth inhibition. These results indicated that the regulation of $TGF-\beta$ receptor expression as well, prior to $TGF-\beta1$ expression, may be involved in the antiproliferative activity of soy isoflavones. Little or no expression of $TGF-\beta$ receptors was found in the MCF-7 and MDA-MB-231 cells, suggesting refractory properties of the cells to growth inhibitory effect of the $TGF-\beta$. The soy isoflavones can seemingly restore the sensitivity of growth inhibitory responses to $TGF-\beta1$ by re-inducing $TGF-\beta$ receptors expression. In conclusions, our findings presented in this study show that the antitumorigenic activity of the soy isoflavones could be mediated by not only $TGF-\beta1$induction but $TGF-\beta$ receptor restoration. Thus, soy isoflavones could be good model molecules to develop new nonsteroidal antiestrogenic chemopreventive agents, associated with, regulation of $TGF-\beta$ and its receptors.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.164-172
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• 1996

Background : Transforming growth factor-$\beta$(TGF-$\beta$) may play a role in a variety of fibroproliferative disorders including pulmonary fibrosis via the induction of extracellular matrix accumulation. TGF-$\beta$ not only stimulates extracellular matrix production, but also decreases matrix degradation. Interstial lung diseases have demonstrated marked expression of TGF-$\beta$. Methods : To evaluate the possible role of TGF-$\beta$ in human pulmonary fibrosis, by using neutralizing antibody of TGF-$\beta$ we investigated immunohistochemically the expression of TGF-$\beta$ in the formalin-fixed, paraffin-embedded tissue sections of the 5 normal cases for the control, and a couple of pieces of tissues taken out of 3 cases with idiopathic pulmonary fibrosis, 3 cases with ILD from bleomycin toxicity, 3 cases with ILD from sarcoidosis, and 3 cases with ILD from eosinophilic granuloma. Results : In the 5 normal cases for the control, the TGF-$\beta$ was expressed in bronchial and alveolar epithelial cells. Up-regulation of the TGF-$\beta$ expression was showed in the interstitial fibroblast cells of alveolar septa in 5 pieces and proliferated alveolar pneumocytes in 1 piece among 6 pieces tissues taken out of 3 cases with idiopathic pulmonary fibrosis. Also up-regulation of the TGF-$\beta$ expression was showed in alveolar lining pneumocytes, intra-alveolar mononuclear cells, and epithelioid cells in most of cases of ILD from bleomycin toxicity, sarcoidosis and eosinophilic granuloma. Conclusion : These findings suggest that up-regulation of the TGF-$\beta$are involved in pathogenesis of interstitial lung fibrosis from variety of causes.

• BMB Reports
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• v.50 no.8
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• pp.429-434
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• 2017

Endometriosis is the abnormal growth of endometrial cells outside the uterus, causing pelvic pain and infertility. Furthermore, adhesion of endometrial tissue fragments to pelvic mesothelium is required for the initial step of endometriosis formation outside uterus. $TGF-{\beta}1$ and adhesion molecules importantly function for adhesion of endometrial tissue fragments to mesothelium outside uterus. However, the function of $TGF-{\beta}1$ on the regulation of adhesion molecule expression for adhesion of endometrial tissue fragments to mesothelium has not been fully elucidated. Interestingly, transforming growth factor ${\beta}1$ ($TGF-{\beta}1$) expression was higher in endometriotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to mesothelial cells was also higher than that of normal endometrial cells. Moreover, $TGF-{\beta}1$ directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of ${\alpha}V$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ via the activation of the $TGF-{\beta}1/TGF-{\beta}RI/Smad2$ signaling pathway. Conversely, the adhesion of $TGF-{\beta}1-stimulated$ endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific $TGF-{\beta}1-mediated$ integrins ${\alpha}V$, ${\beta}1$, and ${\beta}4$ on the endometrial cell membrane. Taken together, these results suggest that $TGF-{\beta}1$ may act to promote the initiation of endometriosis by enhancing integrin-mediated cell-cell adhesion.

• The korean journal of orthodontics
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• v.28 no.2 s.67
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• pp.311-327
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• 1998

The purpose of this study was to evaluate the effects of Transforming Growth Factor-${\beta}$ (TGF-${\beta}$) on the viability of human periodontal ligament cells, in-vitro and on the experimental tooth movement in rat, in-vivo. Human periodontal ligaments were cultured from the first premolar tooth extracted for the purpose of the orthodontic treatment. 0.1, 1, 5 and 10ng/m1 of TGF-${\beta}$ was given to the cultured wells, respectively and the viability was evaluated by MTT assay. Twenty Sprague-Dawley rats were divided into 5 experimental groups(4 rats in each) where 100g of force was applied from helical spring across the maxillary incisors. TGF-${\beta}$ was injected via Hamilton syringe into the periodontal ligament at the mesial and the distal surface of a maxillary incisor of 2 rats in each experimental group. Phosphate buffer saline(PBS) was injected in 2 other rats as controls. Experimental groups were sacrificed at 1, 3, 7, 14 and 28 days after force application, respectively. The obtained tissues were evaluated histologically. The obtained results were as follows: 1. The viability of periodontal ligament cells in 0.1ng/ml of TGF-${\beta}$ was not significantly different from that of control at 1-, 2- and 3-day of cultivation. 2. The viability of periodontal ligament cells was significantly increased at 3-day in 1ng/ml or 5ng/ml of TGF-${\beta}$, and at 2-,3-day in 10ng/ml of of TGF-${\beta}$. 3. The zone of hyalinization in periodontal ligament in pressure side was smaller in TGF-${\beta}$ injection group than that in control group at 3-day after the application of experimental force in rat. But no difference was seen after 7-day. 4. Osteoclastic activity and capillary prolieferation in pressure side were greater in TGF-${\beta}$ injection group than that in control group at 3-day to 7-day. 5. Osteoblastic activity and new bone fomation in tension side were greater in TGF-${\beta}$ injection group than that in control group at 3-day to 14-day.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.216.1-216.1
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• 2001

• Microbiology and Biotechnology Letters
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• v.25 no.2
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• pp.137-143
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• 1997

Porcine transforming growth factor-$\beta$1 (TGF-$\beta$1) was expressed in Escherichia coli using cDNA of TGF-$\beta$1 and glutathione S-transferase (GST) fusion vector pGEX-1$\lambda$T. An ApoI-Tth111I fragment of cDNA which correspond to the amino acid residues from 123 to 390 of the precursor TGF-$\beta$1 was inserted into EcoRI-Tth111I digested pGEM#-l$\lambda$T and the recombined plasmid was named pGET-12. Gene products from the cloned regions of the recombinant plasmids pGET-12 was not detected in soluble fraction of cell free extract but detected in insoluble fraction. The solubilization of insoluble gene product was achieved by the treatment of N-laurylsarcosine. Molecular weight of partially purified proteins determined by electrophoresis was same as expected from cloned fragment. The ELISA test results of the purified proteins showed that immunologically detectable epitope was preserved in recombinant protein.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.69-69
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• 2003

Although effect of TGF$\beta$$_1$ on preimplantation embryo development was reported at mice, little information relevant to this subject is known in bovine. The objectives of this study were to investigate TGF$\beta$$_1$, and TGF$\beta$$_1$ receptors type I and II expression, known as important factors in the embryo development, at unfertilized oocytes and fertilized embryos that will be used as basic data to be compared to NT embryos. We postulated that TGF$\beta$$_1$ may have a beneficial effect on the preimplantation embryo and show different expression patterns as embryo stages change. We have used immunocytochemistry to investigate the presence in unfertilized oocytes and preimplantation embryos of TGF$\beta$$_1$ and the essential components of the TGF$\beta$$_1$ signalling pathway, TGF$\beta$$_1$ receptors type I and II. We found that both receptors, as well as TGF$\beta$$_1$, were present in the unfertilized oocytes. This indicates that TGF$\beta$$_1$, is a maternally expressed protein. At the morulae and blastocyst stages the TGF$\beta$$_1$ receptor type II was not present, but the TGF$\beta$$_1$ receptor type I was present at both stages and we can confirm the TGF$\beta$$_1$ expression of high level at 8-cell stage. These findings support our hypothesis that the TGF$\beta$$_1$, and TGF$\beta$$_1$ receptors may interact with the oocyte and preimplantation embryo, and that TGF$\beta$$_1$ signalling may be important for the development of the oocyte and the preimplahtation embryo.