Ryu-Ichiro Hata - Academia.edu (original) (raw)
Papers by Ryu-Ichiro Hata
Neoplasia, Dec 1, 2010
The expression of p63 (TP63/p51) occurs in the basal cells of stratified epithelia and is strongl... more The expression of p63 (TP63/p51) occurs in the basal cells of stratified epithelia and is strongly enhanced at the early stages of squamous cell carcinomas (SCCs) of the head and neck, skin, cervix, and others. We analyzed a promoter/ enhancer region (2kΔN) that drives the predominant expression of ΔNp63 for sensitivity to Smad signaling pathways. Reporter assays in HepG2 cells showed a moderate activation of 2kΔN by Smad2 and IκB kinase α (IKKα), partners of the newly identified keratinocyte-specific transforming growth factor β (TGF-β) signaling, but not by other Smad molecules. In A431 cells, 2kΔN was activated by Smad2 and IKKα, for which a Smad binding element (SMD2) at −204 was essential. Binding of Smad2 to the chromosomal SMD2 site was detectable. The association of Smad2 with IKKα was evident in the nucleus of A431, accounting for the enhancement of ΔNp63 expression by TGF-β. Moreover, both ΔNp63 and IKKα were necessary to maintain the noninvasive phenotype of this cell line. FaDu, an invasive, Smad4-deficient SCC, also allowed 2kΔN transactivation by transfected Smad2 in the presence of endogenous IKKα. Reflecting the lack of chromosomal SMD2-Smad2 association and the absence of nuclear IKKα, however, endogenous ΔNp63 was not controlled by TGF-β or IKKα in FaDu. SCC tissue arrays showed nuclear accumulation of IKKα and p63 intensification in well-differentiated noninvasive lesions. This study indicates that p63 is a target gene of the proposed keratinocyte-specific TGF-β signal pathway for suppression of the malignant conversion of SCC.
European journal of biochemistry, Jun 1, 1988
Collagen synthesis was examined in skin fibroblasts from a patient with a variant of Ehlers-Danlo... more Collagen synthesis was examined in skin fibroblasts from a patient with a variant of Ehlers-Danlos syndrome. The relative rate of collagen synthesis to total protein synthesis in the patient's fibroblasts was always one-half of that in fibroblasts from normal controls. Total collagen synthesis, as assessed by quantification of total hydroxyproline, was also significantly lower than that of controls, indicating that the rate of collagen synthesis by the patient's fibroblasts was decreased compared with that by normal fibroblasts. Analysis of procollagen and collagen components showed the absence of the pro alpha 2(I) chain and its derivatives. Dot-blot and Northern-blot analyses showed the patient's fibroblasts to contain less than 10% of the mRNAs for pro alpha 2(I) found in control fibroblasts. In spite of these results, Southern blot analysis of genomic DNA indicated the presence of the same number of genes for the pro alpha 2(I) collagen chain in the patient's fibroblasts as in control fibroblasts, suggesting malfunctioning pro alpha 2(I) collagen genes as the cause for failure of the patient's fibroblasts to synthesize pro alpha 2(I) collagen chains.
Japanese Circulation Journal-english Edition, Jan 20, 1973
Connective tissue, Mar 25, 2001
Type 1 collagen is the major structural protein of the extracellular matrix and is found in large... more Type 1 collagen is the major structural protein of the extracellular matrix and is found in large quantities in various part of the body, especially in the connective tissues such as the skin, bones, teeth, and tendons. A decrease in the rate of type 1 collagen synthesis or production of defective molecules induces deformity of embryos or fetuses in extreme cases, as occurs in the patients with Ehlers-Danlos syndrome (EDS) or osteogenesis imperfecta (01) 1-3). On the other hand, aberrant accumulation of type 1 collagen in tissue and organs results in organ fibrosis such as hepatic fibrosis in the liv巴r,pulmonary fibrosis in the lung, and systemic sc¥erosis (SSc) in the skin),4). These facts indicate that expression oftype 1 collagen gen巴sare precisely regulated both during th巴courseof development and for maintenance of homeostasis of th巴body in normal subjects. Recent自ndingofthe polymorphisms ofthe human genome and their possible functions in the regulation of the respective genes suggests that polymorphism of type 1 collagen genes might be responsible for the predisposition toward various connective tissue disorders in addition to hereditary diseases.
Connective tissue, Jun 1, 2003
Analysis of extracellular matrix of a skin tumor from patients with juvenile hyaline fibromatosis... more Analysis of extracellular matrix of a skin tumor from patients with juvenile hyaline fibromatosis keisuke Tanak~l , Tetsuya Ebihara, Shunji Ha伽 jl,Eijiro Adache, Ryu・IchiroHata3, M部 amiArai4, Noriyoshi Kawaguchi4, Hiroaki Kandaヲ JojiUtsunomiya 4, Yoshio Miki 4, Michiaki Hiramot05 ラ Shinkichi Irie lNippi Research Ins封印鉛 ofBioma廿lXヲ 2KitasatoUniversi帆 3KanagawaDental College, 4Cancer Institute Hospitalラ5SaiseikaiN akatsu Hospital
Nishinihon Journal of Urology, 1992
![Research paper thumbnail of [Functional alterations of human platelets following 111In labeling with different ligands and incubation media]](https://attachments.academia-assets.com/118061337/thumbnails/1.jpg)
](PubMed, May 1, 1990
We studied the effects of various 111In-water soluble chelates and incubation media on labeling e... more We studied the effects of various 111In-water soluble chelates and incubation media on labeling efficiency of platelets and in vitro platelet aggregability. High labeling efficiency of platelets in ACD-saline was achieved with 111In-oxine sulfate, 111In-tropolone and 111In-MPO (2-mercaptopyridine-N-oxide). In the condition with 4.8 x 10(6)/mm3 platelets in ACD-plasma, 111In-oxine-sulfate had low labeling efficiency and inconsistent labeling, while 111In-tropolone and 111In-MPO had high labeling efficiency. In vitro platelet aggregability (ADP 2 microM) was reduced when platelets were labeled in the absence of plasma. However, there was no significant difference in platelet aggregability among 111In-platelets labeled by three different chelates. In conclusion, to maintain aggregation activity of the platelets with relatively high labeling efficiency, the best result was obtained by using MPO or tropolone chelate in plasma at 4.8 x 10(6)/microliters platelet concentration.
Connective tissue, Mar 25, 1998
PubMed, 1984
Following intraperitoneal injection of [3H]proline and colchicine, rat liver cells were dispersed... more Following intraperitoneal injection of [3H]proline and colchicine, rat liver cells were dispersed by collagenase perfusion and fractionated by low-speed and density gradient centrifugation. Analysis of the collagenous components using purified bacterial collagenase showed that 0.1 to 0.2% of the labeled protein produced by the liver cells was collagen. Considering the population of the hepatocytes in the liver (70%), 80% of the collagen produced by the liver could be attributed to the hepatocytes.
Cell Biology International Reports, Jun 1, 1990
Biochemical and Biophysical Research Communications, Apr 1, 2012
The chemokine BRAK/CXCL14 (BRAK) is expressed in normal squamous epithelium, but is not expressed... more The chemokine BRAK/CXCL14 (BRAK) is expressed in normal squamous epithelium, but is not expressed or is expressed at negligible levels in head and neck squamous cell carcinoma. Malignant cells are known to be dedifferentiated compared with normal epithelial cells, suggesting a role for differentiation cues in the expression of BRAK. Thus, we examined the relationship between BRAK expression and stages of differentiation level in epithelial cells. Immunohistochemical analysis showed that BRAK protein was expressed in cells above the spinous cell layer in normal epithelia. In HSC-3 cells in culture, expression of BRAK mRNA was significantly upregulated by cell contact in a cell density-dependent manner, and mRNA expression of cell differentiation markers such as involucrin, cystatin-A, TGM1, TGM3, and TGM5 was concomitantly augmented. Furthermore, the upregulation of BRAK induced by cell contact was suppressed by chlorpromazine, a specific inhibitor of calmodulin. We previously reported that GC boxes and a TATA-like sequence in the BRAK promoter region are associated with the expression of BRAK. Using a promoter assay and ChIP, we demonstrated that binding of the stimulating protein-1 (SP1) transcription factor to a GC box upstream of the BRAK transcription start site was necessary for cell densitydependent upregulation of BRAK. These results indicated that upregulation of BRAK was accompanied by differentiation of epithelial cells induced by calcium/calmodulin signaling, and that SP1 binding to the BRAK promoter region played an important role in this signaling.
Pathology International, Jul 1, 1981
Type specific rabbit antibodies to bovine type I, II, III, and IV (basement membrane) collagens s... more Type specific rabbit antibodies to bovine type I, II, III, and IV (basement membrane) collagens showing no cross-reaction with other types of collagen were prepared by cross-adsorption and diethylaminoethyl-cellulose chromatography. The antibodies to bovine type I and III collagens showed a high cross-reaction with the corresponding human collagens, but those to type II and IV collagens did moderate and no cross-reactions with human type II and IV collagens, respectively. By using these antibodies, tissue distribution of various types of collagen in normal bovine lung was examined by indirect immunofluorescence microscopy. both type I and III collagens were found to distribute widely in the interstitium of bronchial tree, bronchial lamina propria and of interlobules as well as alveolar nipples and adventitia of pulmonary arteries. Type II collagen was located only in bronchial cartilage. The tissues mainly stained for type III collagen were the alveolar interstitium (also stained faintly for type I collagen) and the intima and media of the arteries. Type IV collagen was located in a membranous fashion in alveolar septa and bronchial smooth muscles and subepithelial layers as well as capillaries and the intima and media of arteries.
Transgenic Research, Mar 24, 2010
We reported previously that the forced expression of the chemokine BRAK, also called CXCL14 in he... more We reported previously that the forced expression of the chemokine BRAK, also called CXCL14 in head and neck squamous cell carcinoma (HNSCC) cells decreased the rate of tumor formation and size of tumor xenografts compared with mock-vector treated cells in athymic nude mice or in severe combined immunodeficiency mice. This suppression occurred even though the growth rates of these cells were the same under in vitro culture conditions, suggesting that a high expression level of the gene in tumor cells is important for the suppression of tumor establishment in vivo. The aim of this study was to determine whether CXCL14/BRAK transgenic mice show resistance to tumor cell xenografts or not. CXCL14/BRAK cDNA was introduced into male C57BL/6 J pronuclei, and 10 founder transgenic mice (Tg) were obtained. Two lines of mice expressed over 10 times higher CXCL14/BRAK protein levels (14 and 11 ng/ml plasma, respectively) than normal blood level (0.9 ng/ml plasma), without apparent abnormality. The sizes of Lewis lung carcinoma and B16 melanoma cell xenografts in Tg mice were significantly smaller than those in control wild-type mice, indicating that CXCL14/BRAK, first found as a suppressor of tumor progression of HNSCC, also suppresses the progression of a carcinoma of other tissue origin. Immunohistochemical studies showed that invasion of blood vessels into tumors was suppressed in tumor xenografts of CXCL14/BRAK Tg mice. These results indicate that CXCL14/BRAK suppressed tumor cell xenografts by functioning paracrine or endocrine fashion and that CXCL14/BRAK is a very promising molecular target for tumor suppression without side effects.
Cell Biology International, 1996
Morphogenesis is an old, and one of the latest, fascinating fields in biological science and a hu... more Morphogenesis is an old, and one of the latest, fascinating fields in biological science and a huge number of papers on molecular mechanisms underlying it have been published. But most of the works and reviews on these mechanisms pertain to molecules of, as it were, the planning or design of morphogenesis, such as morphogens and homeodomain proteins. In this review, I will describe the function of extracellular matrix (ECM) and other cell adhesion molecules in morphogenesis as that of actual morpho‐creating molecules, morphocreators, and discuss their roles as positional information‐pertaining molecules.
Neoplasia, Dec 1, 2010
The expression of p63 (TP63/p51) occurs in the basal cells of stratified epithelia and is strongl... more The expression of p63 (TP63/p51) occurs in the basal cells of stratified epithelia and is strongly enhanced at the early stages of squamous cell carcinomas (SCCs) of the head and neck, skin, cervix, and others. We analyzed a promoter/ enhancer region (2kΔN) that drives the predominant expression of ΔNp63 for sensitivity to Smad signaling pathways. Reporter assays in HepG2 cells showed a moderate activation of 2kΔN by Smad2 and IκB kinase α (IKKα), partners of the newly identified keratinocyte-specific transforming growth factor β (TGF-β) signaling, but not by other Smad molecules. In A431 cells, 2kΔN was activated by Smad2 and IKKα, for which a Smad binding element (SMD2) at −204 was essential. Binding of Smad2 to the chromosomal SMD2 site was detectable. The association of Smad2 with IKKα was evident in the nucleus of A431, accounting for the enhancement of ΔNp63 expression by TGF-β. Moreover, both ΔNp63 and IKKα were necessary to maintain the noninvasive phenotype of this cell line. FaDu, an invasive, Smad4-deficient SCC, also allowed 2kΔN transactivation by transfected Smad2 in the presence of endogenous IKKα. Reflecting the lack of chromosomal SMD2-Smad2 association and the absence of nuclear IKKα, however, endogenous ΔNp63 was not controlled by TGF-β or IKKα in FaDu. SCC tissue arrays showed nuclear accumulation of IKKα and p63 intensification in well-differentiated noninvasive lesions. This study indicates that p63 is a target gene of the proposed keratinocyte-specific TGF-β signal pathway for suppression of the malignant conversion of SCC.
European journal of biochemistry, Jun 1, 1988
Collagen synthesis was examined in skin fibroblasts from a patient with a variant of Ehlers-Danlo... more Collagen synthesis was examined in skin fibroblasts from a patient with a variant of Ehlers-Danlos syndrome. The relative rate of collagen synthesis to total protein synthesis in the patient's fibroblasts was always one-half of that in fibroblasts from normal controls. Total collagen synthesis, as assessed by quantification of total hydroxyproline, was also significantly lower than that of controls, indicating that the rate of collagen synthesis by the patient's fibroblasts was decreased compared with that by normal fibroblasts. Analysis of procollagen and collagen components showed the absence of the pro alpha 2(I) chain and its derivatives. Dot-blot and Northern-blot analyses showed the patient's fibroblasts to contain less than 10% of the mRNAs for pro alpha 2(I) found in control fibroblasts. In spite of these results, Southern blot analysis of genomic DNA indicated the presence of the same number of genes for the pro alpha 2(I) collagen chain in the patient's fibroblasts as in control fibroblasts, suggesting malfunctioning pro alpha 2(I) collagen genes as the cause for failure of the patient's fibroblasts to synthesize pro alpha 2(I) collagen chains.
Japanese Circulation Journal-english Edition, Jan 20, 1973
Connective tissue, Mar 25, 2001
Type 1 collagen is the major structural protein of the extracellular matrix and is found in large... more Type 1 collagen is the major structural protein of the extracellular matrix and is found in large quantities in various part of the body, especially in the connective tissues such as the skin, bones, teeth, and tendons. A decrease in the rate of type 1 collagen synthesis or production of defective molecules induces deformity of embryos or fetuses in extreme cases, as occurs in the patients with Ehlers-Danlos syndrome (EDS) or osteogenesis imperfecta (01) 1-3). On the other hand, aberrant accumulation of type 1 collagen in tissue and organs results in organ fibrosis such as hepatic fibrosis in the liv巴r,pulmonary fibrosis in the lung, and systemic sc¥erosis (SSc) in the skin),4). These facts indicate that expression oftype 1 collagen gen巴sare precisely regulated both during th巴courseof development and for maintenance of homeostasis of th巴body in normal subjects. Recent自ndingofthe polymorphisms ofthe human genome and their possible functions in the regulation of the respective genes suggests that polymorphism of type 1 collagen genes might be responsible for the predisposition toward various connective tissue disorders in addition to hereditary diseases.
Connective tissue, Jun 1, 2003
Analysis of extracellular matrix of a skin tumor from patients with juvenile hyaline fibromatosis... more Analysis of extracellular matrix of a skin tumor from patients with juvenile hyaline fibromatosis keisuke Tanak~l , Tetsuya Ebihara, Shunji Ha伽 jl,Eijiro Adache, Ryu・IchiroHata3, M部 amiArai4, Noriyoshi Kawaguchi4, Hiroaki Kandaヲ JojiUtsunomiya 4, Yoshio Miki 4, Michiaki Hiramot05 ラ Shinkichi Irie lNippi Research Ins封印鉛 ofBioma廿lXヲ 2KitasatoUniversi帆 3KanagawaDental College, 4Cancer Institute Hospitalラ5SaiseikaiN akatsu Hospital
Nishinihon Journal of Urology, 1992
PubMed, May 1, 1990
We studied the effects of various 111In-water soluble chelates and incubation media on labeling e... more We studied the effects of various 111In-water soluble chelates and incubation media on labeling efficiency of platelets and in vitro platelet aggregability. High labeling efficiency of platelets in ACD-saline was achieved with 111In-oxine sulfate, 111In-tropolone and 111In-MPO (2-mercaptopyridine-N-oxide). In the condition with 4.8 x 10(6)/mm3 platelets in ACD-plasma, 111In-oxine-sulfate had low labeling efficiency and inconsistent labeling, while 111In-tropolone and 111In-MPO had high labeling efficiency. In vitro platelet aggregability (ADP 2 microM) was reduced when platelets were labeled in the absence of plasma. However, there was no significant difference in platelet aggregability among 111In-platelets labeled by three different chelates. In conclusion, to maintain aggregation activity of the platelets with relatively high labeling efficiency, the best result was obtained by using MPO or tropolone chelate in plasma at 4.8 x 10(6)/microliters platelet concentration.
Connective tissue, Mar 25, 1998
PubMed, 1984
Following intraperitoneal injection of [3H]proline and colchicine, rat liver cells were dispersed... more Following intraperitoneal injection of [3H]proline and colchicine, rat liver cells were dispersed by collagenase perfusion and fractionated by low-speed and density gradient centrifugation. Analysis of the collagenous components using purified bacterial collagenase showed that 0.1 to 0.2% of the labeled protein produced by the liver cells was collagen. Considering the population of the hepatocytes in the liver (70%), 80% of the collagen produced by the liver could be attributed to the hepatocytes.
Cell Biology International Reports, Jun 1, 1990
Biochemical and Biophysical Research Communications, Apr 1, 2012
The chemokine BRAK/CXCL14 (BRAK) is expressed in normal squamous epithelium, but is not expressed... more The chemokine BRAK/CXCL14 (BRAK) is expressed in normal squamous epithelium, but is not expressed or is expressed at negligible levels in head and neck squamous cell carcinoma. Malignant cells are known to be dedifferentiated compared with normal epithelial cells, suggesting a role for differentiation cues in the expression of BRAK. Thus, we examined the relationship between BRAK expression and stages of differentiation level in epithelial cells. Immunohistochemical analysis showed that BRAK protein was expressed in cells above the spinous cell layer in normal epithelia. In HSC-3 cells in culture, expression of BRAK mRNA was significantly upregulated by cell contact in a cell density-dependent manner, and mRNA expression of cell differentiation markers such as involucrin, cystatin-A, TGM1, TGM3, and TGM5 was concomitantly augmented. Furthermore, the upregulation of BRAK induced by cell contact was suppressed by chlorpromazine, a specific inhibitor of calmodulin. We previously reported that GC boxes and a TATA-like sequence in the BRAK promoter region are associated with the expression of BRAK. Using a promoter assay and ChIP, we demonstrated that binding of the stimulating protein-1 (SP1) transcription factor to a GC box upstream of the BRAK transcription start site was necessary for cell densitydependent upregulation of BRAK. These results indicated that upregulation of BRAK was accompanied by differentiation of epithelial cells induced by calcium/calmodulin signaling, and that SP1 binding to the BRAK promoter region played an important role in this signaling.
Pathology International, Jul 1, 1981
Type specific rabbit antibodies to bovine type I, II, III, and IV (basement membrane) collagens s... more Type specific rabbit antibodies to bovine type I, II, III, and IV (basement membrane) collagens showing no cross-reaction with other types of collagen were prepared by cross-adsorption and diethylaminoethyl-cellulose chromatography. The antibodies to bovine type I and III collagens showed a high cross-reaction with the corresponding human collagens, but those to type II and IV collagens did moderate and no cross-reactions with human type II and IV collagens, respectively. By using these antibodies, tissue distribution of various types of collagen in normal bovine lung was examined by indirect immunofluorescence microscopy. both type I and III collagens were found to distribute widely in the interstitium of bronchial tree, bronchial lamina propria and of interlobules as well as alveolar nipples and adventitia of pulmonary arteries. Type II collagen was located only in bronchial cartilage. The tissues mainly stained for type III collagen were the alveolar interstitium (also stained faintly for type I collagen) and the intima and media of the arteries. Type IV collagen was located in a membranous fashion in alveolar septa and bronchial smooth muscles and subepithelial layers as well as capillaries and the intima and media of arteries.
Transgenic Research, Mar 24, 2010
We reported previously that the forced expression of the chemokine BRAK, also called CXCL14 in he... more We reported previously that the forced expression of the chemokine BRAK, also called CXCL14 in head and neck squamous cell carcinoma (HNSCC) cells decreased the rate of tumor formation and size of tumor xenografts compared with mock-vector treated cells in athymic nude mice or in severe combined immunodeficiency mice. This suppression occurred even though the growth rates of these cells were the same under in vitro culture conditions, suggesting that a high expression level of the gene in tumor cells is important for the suppression of tumor establishment in vivo. The aim of this study was to determine whether CXCL14/BRAK transgenic mice show resistance to tumor cell xenografts or not. CXCL14/BRAK cDNA was introduced into male C57BL/6 J pronuclei, and 10 founder transgenic mice (Tg) were obtained. Two lines of mice expressed over 10 times higher CXCL14/BRAK protein levels (14 and 11 ng/ml plasma, respectively) than normal blood level (0.9 ng/ml plasma), without apparent abnormality. The sizes of Lewis lung carcinoma and B16 melanoma cell xenografts in Tg mice were significantly smaller than those in control wild-type mice, indicating that CXCL14/BRAK, first found as a suppressor of tumor progression of HNSCC, also suppresses the progression of a carcinoma of other tissue origin. Immunohistochemical studies showed that invasion of blood vessels into tumors was suppressed in tumor xenografts of CXCL14/BRAK Tg mice. These results indicate that CXCL14/BRAK suppressed tumor cell xenografts by functioning paracrine or endocrine fashion and that CXCL14/BRAK is a very promising molecular target for tumor suppression without side effects.
Cell Biology International, 1996
Morphogenesis is an old, and one of the latest, fascinating fields in biological science and a hu... more Morphogenesis is an old, and one of the latest, fascinating fields in biological science and a huge number of papers on molecular mechanisms underlying it have been published. But most of the works and reviews on these mechanisms pertain to molecules of, as it were, the planning or design of morphogenesis, such as morphogens and homeodomain proteins. In this review, I will describe the function of extracellular matrix (ECM) and other cell adhesion molecules in morphogenesis as that of actual morpho‐creating molecules, morphocreators, and discuss their roles as positional information‐pertaining molecules.