• Journal of Chest Surgery
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• v.43 no.4
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• pp.394-398
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• 2010

Background: The overexpression of transforming growth factor-beta 1 receptor II (TGF-${\beta}1$RII) and transforming growth factor-beta 1 (TGF-${\beta}1$) ligand may be involved in the formation of a bulla. In this study, we tested if serum TGF-${\beta}1$ ligand levels correlated with the expression level of TGF-${\beta}1$RII and TGF-${\beta}1$ in bullous tissues from patients with spontaneous pneumothorax. Material and Method: Bullous lung tissues and blood samples were obtained from 19 patients with spontaneous pneumothorax, 18 males and 1 female, aged 17 to 35 years old. The bullous tissues were obtained by video-assisted thoracic surgery (VATS), fixed in formalin, embedded in paraffin, and cut into $5{\sim}6{\mu}m$ thick slices. Sections were immunohistochemically stained with primary antibodies against TGF-${\beta}1$ or TGF-${\beta}1$RII, and serum levels of TGF-${\beta}1$ in patients and normal controls was measured by enzyme-linked immunosorbent assay (ELISA). Result: Of the 19 patients, 16 were TGF-${\beta}1$ positive and 10 were TGF-${\beta}1$RII positive. Among the 16 TGF-${\beta}1$ positives, 9 were also TGF-${\beta}1RII$ positive. As seen previously, strong immunohistochemical staining of TGF-${\beta}1$RII and TGF-${\beta}$ was detected in the boundary region between the bullous and normal lung tissues. Average TGF-${\beta}1$ blood levels of both TGF-${\beta}1$ and TGF-${\beta}1$RII positive patients was $38.36{\pm}16.2ng/mL$, and that of five controls was $54.06{\pm}15ng/mL$. Conclusion: These results suggest that overexpression of TGF-${\beta}1$ and TGF-${\beta}1$RII expression may be involved in the formation of bullae. TGF-${\beta}1$ blood levels in patients with primary spontaneous pneumothorax is lower than normal people, suggesting that the high level of local TGF-${\beta}1$ expression in the bullous tissue region, but not in the whole blood, may contribute more in the formation of bullae.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.142-142
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• 2003

Transforming growth factor (TGF)-${\beta}$, a hormonally active polypeptide found in normal and transformed tissue, is a potent regulator of cell growth and differentiation. In this study, we examined the effect of TGF-${\beta}$ on invasion and motility of MCF10A human breast epithelial cells. TGF-${\beta}$ induced migration and invasive phenotype of the parental MCF10A cells in a dose-dependent manner.(omitted)

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.805-809
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• 2006

Background: In our previous study, we demonstrated that transforming growth factor-beta 1 receptor II(TGF-${\beta}1RII$) may have a role in the formation of bullae. In this study, we investigated if expression of transforming growth factor-beta 1 (TGF-${\beta}1$) ligand was altered in a bullous lung tissue by immunohistochemical staining of bullous tissues from patients with primary spontaneous pneumothorax. Material and Method: Bullous lung tissues were obtained from 36 patients with primary spontaneous pneumothorax, including 34 males and 2 females aged 14 to 38 years old. Result: Of the 36 patients, 19 were TGF-${\beta}1$ positive and 24 were transforming growth factor-beta 1 receptor II(TGF-${\beta}1RII$) positive. Among the 19 TGF-${\beta}1$ positives, 15 were also TGF-${\beta}1RII$ positive, observation at high magnification showed that strong immunohistochemical stain was detected in the boundary region between the bullous and normal lung tissues. Conclusion: These results suggest that overexpression of TGF-${\beta}1$ may be involved in the formation of a bulla as well as the alteration of TGF-${\beta}1RII$ expression. Further molecular studies are needed to elucidate the more detailed molecular mechanisms of the bulla formation.

• BMB Reports
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• v.38 no.1
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• pp.1-8
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• 2005

Transforming growth factor-$\beta$ is a pleiotropic growth factor that has enthralled many investigators for approximately two decades. In addition to many reports that have clarified the basic mechanism of transforming growth factor-$\beta$ signal transduction, numerous laboratories have published on the clinical implication/application of transforming growth factor-$\beta$. To name a few, dysregulation of transforming growth factor-$\beta$ signaling plays a role in carcinogenesis, autoimmunity, angiogenesis, and wound healing. In this report, we will review these clinical implications of transforming growth factor-$\beta$.

• Biomedical Science Letters
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• v.5 no.2
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• pp.181-190
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• 1999

To evaluate the usefulness of transforming growth factor-$\beta$1 (TGF-$\beta$1) as a new tumor marker, we determined the plasma TGF-$\beta$1 levels using sandwich ELISA assay in cancer patients. Patients with three most common adult cancers in Korea (stomach, liver and breast cancer) and children's cancers (leukemia and two kinds of solid tumor) were enrolled for the study. Furthermore, 39 individuals were subjected to age and sex-stratified plasma TGF-$\beta$1 analysis. No statistical difference was demonstrated with respect to age or sex. The mean plasma TGF-$\beta$1 level (16.0 ng/ ml) of stomach cancer patients was significantly higher than that (8.3 ng/ml) of controls. However, there was no difference among the mean plasma TGF-$\beta$1 levels of liver, breast cancer patients and controls. Seven of 16 patients (43.7%) with stomach cancer, one of 8 (12.5%) with liver cancer, and one of 7 (14.3%) with breast cancer showed higher TGF-$\beta$1 levels compared to controls. Plasma TGF-$\beta$1 concentrations of five leukemic children remained in the normal range regardless of the remission state. In contrast, initial high TGF-$\beta$1 levels from two children with solid tumors returned to normal range on surgical resection of tumors. From the above results, we could conclude that plasma TGF-$\beta$1 levels of apparently healthy individuals seem to be rather constant irrespective of difference in age or sex, and the plasma TGF-$\beta$1 has the limited value as a screening test for the diagnosis of aforementioned adult cancers because of its low sensitivity. Finally, additional studies need to be pursed for the large number of stomach cancer and pediatric solid tumor patients in order to reach a secure conclusion on the usefulness of plasma TGF-$\beta$1 as a tumor marker in these patients.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.143-150
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• 2001

Background : Many investigators have found transforming growth factor-${\beta}1$ (TGF-${\beta}1$) to be elevated in tumors. Changes in responsiveness to TGF-${\beta}1$ have been linked to malignant transformation, tumor progression and tumor regression. Many malignant cell lines of epithelial or hematopoietic origin are refractory to the antiproliferative effects of TGF-${\beta}1$. However, a little is known about the association of TGF-${\beta}1$ with progression of malignant tumor. Methods : In this study, we measured the plasma level of TGF-${\beta}1$ in various cancer patients and evaluated the utility of plasma TGF-${\beta}1$ as a possible tumor marker. Plasma TGF-${\beta}1$ levels were measured using enzyme-linked immunosorbent assay in cancer patients and normal controls. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as tumor marker were compared with TGF-${\beta}1$ in the aspects of sensitivity and specificity. Results : The mean of plasma TGF-${\beta}1$ levels was $1.219{\pm}0.834ng/ml$ in normal controls, $5.491{\pm}3.598ng/ml$ in breast cancer, $12.670{\pm}10.386ng/ml$ in lung cancer, $5.747{\pm}3.228ng/ml$ in hepatocellular carcinoma and $10.854{\pm}7.996ng/ml$ in cervical cancer. In comparison with CEA and AFP, TGF-${\beta}1$ is more sensitive. Conclusion : We conclude that the high levels of TGF-${\beta}1$ are common in the plasma of cancer patients. These results suggest that the plasma TGF-${\beta}1$ level can be a potent tumor marker in various cancer patients.

• Animal cells and systems
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• v.4 no.3
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• pp.273-278
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• 2000

Transforming growth factor-$\beta$ (IGF-$\beta$)s are multifunctional small polypeptides synthesized in most cell types. TGF-$\beta$ exerts pivotal effects on both bone formation and resorption. In addition, increasing lines of evidence implicate TGF-$\beta$ as a potential coupling factor between these two processes during bone remodeling. In the present study, the expression form and the activation mechanism of latent-TGF-$\beta$ were investigated using specific antibodies for each isoform. TGF-$\beta$s were observed to be synthesized and accumulated in a large amount in cultured osteoblastic cells. The estimated molecular weights of intracellular TGF-$\beta$2 and -$\beta$3 were 49 and 55 kDa, respectively. Based on proteolytic digestion study and immunofluorescence observation, these precursor forms seemed to be accumulated in distinct intracellular compartments. To examine whether the internal pool of TGF-$\beta$ was possiblely regulated by external signals, their biological activites were examined in a conditioned media of this cell. Although the intact conditioned media did not contain detectable TGF-$\beta$ activity, heat-treatment or acid-activation of the conditioned media revealed significant TGF-$\beta$ activity. Furthermore, in the presence of estrogen, this activity was dramatically diminished. It is known that activation of latent TGF-$\beta$ can be achieved by different chemical and enzymatic treatments, or by incubation with certain cell types. This extracellular activation was suggested as a key step in the regulation of TGF-$\beta$ activity. In addition to these extracellular activation, this study suggests that the synthesis and intracellular processing are important regulation steps for TGF-$\beta$ action. In addition, this regulation Is specific for TGF-$\beta$ type 2, because the change was not observed in TGF-$\beta$3 in osteoblastic cell line.

• BMB Reports
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• v.30 no.2
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• pp.119-124
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• 1997

Transforming growth $factor-{\beta}\;(TGF-{\beta})$ is a multifunctional polypeptide that exerts biological roles including cell proliferation, differentiation, extracellular matrix deposition and apoptosis in many different cell types. $TGF-{\beta}$, although known as a negative growth regulator, has not been tested in human embryo lung (HEll cells. This study attempts to understand the role of $TGF-{\beta}$ on growth control of HEL cells in relationship to tyrosine phosphorylation pattern of cellular proteins. In density-arrested HEL cells treated with $TGF-{\beta}$, analysis of Western immunoblot showed induction of tyrosine phosphorylation of two major cellular proteins (15 kDa and 45 kDa). In normal proliferating HEL cells with different concentrations of serum, further analysis indicated that the increase in tyrosine phosphorylation of a 45 kDa protein was regulated in serum concentration-dependent manner. However, in proliferating HEL cells treated with $TGF-{\beta}$, tyrosine phosphorylation of 45 kDa was down-regulated. Calcium involvement in the regulation of tyrosine phosphorylation of 45 kDa and 15 kDa proteins was also examined. Tyrosine phosphorylation of 15 kDa protein but not of 45 kDa protein was regulated by exogenous calcium. The level of tyrosine phosphorylation of 15 kDa protein was low at reduced caclium concentration and high at elevated caclium concentration. $TGF-{\beta}$ reversed the pattern of tyrosine phosphorylation of 15 kDa protein. These results suggest that tyrosine phosphorylation of 45 and 15 kDa proteins in HEL cells may be controlled depending on the physiological status of the cells, i.e., low in arrested cells and high in proliferating cells. And the tyrosine phosphorylation of the two proteins appears to be down- or up-regulated by $TGF-{\beta}$.

• Journal of Life Science
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• v.18 no.4
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• pp.461-466
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• 2008

Transforming growth $factor-{\beta}$ ($TGF-{\beta}$)-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. Gadd45b has been known to participate in $TGF-{\beta}-induced$ apoptosis by the activation of p38 kinase. In this report, we show that Gadd45b is an immediate-early response gene for $TGF-{\beta}$ during apoptosis in EpH4 cells. To elucidate the molecular mechanism of $TGF-{\beta}-induced$ Gadd45b gene expression, we cloned the 5'-flanking region of the mouse Gadd45b gene. When transfected into EpH4 cells, this 5'-flanking region conferred promoter activity and inducibility by $TGF-{\beta}$. Deletion analyses demonstrated that the minimal promoter activity was detected in the proximal region 220 bp upstream of the transcription initiation site. We also found that the proximal Gadd45b promoter is activated by $TGF-{\beta}$ through the action of Smad2, Smad3, and Smad4. Finally, we show that the expression of Gadd45b gene by $TGF-{\beta}$ is suppressed in EpRas cells in which $TGF-{\beta}$ could not induce apoptosis, suggesting that Gadd45b may be a crucial target for $TGF-{\beta}-induced$ apoptosis in EpH4 cells.

• IMMUNE NETWORK
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• v.9 no.4
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• pp.122-126
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• 2009

Transforming growth factor-$\beta$ (TGF-$\beta$) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-$\beta$ facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-$\beta$ antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-$\beta$ antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic $CD8^+$ Tcells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-$\beta$ on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.