Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The differential proteomic approach (2D gel analysis coupled to MALDI-MS analysis) of nuclear proteins can provide an extremely useful tool to understand control of cell proliferation and differentiation. In order to identify possible markers of dedifferentiation between normal and cancerous thyroid cells, we used a differential proteomics approach by comparing nuclear extracts from the normal rat thyroid cell line FRTL-5 and the completely undifferentiated Ki-mol cell line, obtained by transformation with the Ki-ras oncogene. Galectin-3 (Gal-3) was identified as highly expressed, in the nuclear compartment, only in the transformed cell line. By using different human cancer cell lines, we showed that Gal-3 is maximally expressed in nuclei of papillary cancer cells. We focused on the functional relationship existing between Gal-3 and the thyroid-specific transcription factor TTF-1, whose expression is maintained in papillary cancer where it can contribute to the proliferating status. By using gel-retardation and transient tranfection assays, we demonstrate that Gal-3 upregulates the TTF-1 transcriptional activity. GST-pulldown experiments demonstrate the occurrence of interaction between Gal-3 and TTF-1 homeodomain. Since several lines of evidence suggest a role for Gal-3 in controlling proliferation and tumor progression in thyroid cancer, the stimulatory activity played by Gal-3 over TTF-1 would account for a possible molecular mechanism through which the galectin controls proliferation in thyroid cells.
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PMID:Nuclear localization of Galectin-3 in transformed thyroid cells: a role in transcriptional regulation. 1261 69

DMBT1 and galectin-3 are potential interacting proteins with presumably complex roles in tumorigenesis. While at present a variety of mechanisms are discussed for DMBT1 and its participation in cancer, galectin-3 is commonly known to exert tumor-promoting effects. However, in vitro studies in a rodent system have suggested that DMBT1/galectin-3 interaction in the ECM triggers epithelial differentiation, which would point to tumor-suppressive properties. To improve the understanding of DMBT1/galectin-3 action in cancer, we carried out studies in skin cancer of different origins. Mutational analyses of DMBT1 identified a missense mutation in 1 of 13 melanoma cell lines. It led to an exchange of an evolutionary conserved proline residue for serine and located within the second CUB domain of DMBT1. Immunohistochemical analyses demonstrated absence of DMBT1/galectin-3 expression from melanocytes but induction of DMBT1 expression in 1 of 8 nevi and 1 of 11 melanomas and of galectin-3 expression in 3 of 8 nevi and 4 of 8 melanomas. These data suggest that DMBT1 and galectin-3 are unlikely to act as classical tumor suppressors in melanomas. DMBT1 and galectin-3 appear to be secreted to the ECM by epithelial cells within the epidermis and the hair follicle. Compared to the flanking normal epidermis, skin tumors of epithelial origin frequently displayed downregulation of DMBT1 (18 of 19 cases) and galectin-3 (12 of 12 cases). Thus, loss of DMBT1/galectin-3 expression may play a role in the genesis of epithelial skin cancer. This would support the view that galectin-3 can exert tumor-suppressive effects in certain scenarios, and DMBT1/galectin-3-mediated differentiation represents a candidate mechanism for this effect.
Int J Cancer 2003 Jun 10
PMID:Frequent downregulation of DMBT1 and galectin-3 in epithelial skin cancer. 1267 72

Galectin-3 (Gal-3), a beta-galactoside-binding protein, has been implicated in a variety of biological functions, including cell proliferation and differentiation, tumor cell adhesion, angiogenesis, apoptosis, tumor progression, and metastasis. We investigated the role of Gal-3 in the development and progression of pituitary tumors. Immunohistochemical and Western blot analysis of normal and neoplastic human pituitaries showed that only lactotroph (PRL) and corticotroph (ACTH) hormone-producing cells and tumors expressed Gal-3. Gal-3 was present in 24 of 38 (63.2%) PRL adenomas, 5 of 6 (83.3%) PRL carcinomas, 19 of 41 (46.3) ACTH adenomas, and 7 of 8 (87.5%) ACTH carcinomas, but not in 112 other pituitary adenomas and carcinomas. Pituitary folliculo-stellate cells, which have macrophage-type functions in the anterior pituitary, also expressed Gal-3. Hyperplastic and neoplastic pituitaries from p27(Kip1) (p27)-null mice, which produce mainly ACTH, showed increased Gal-3 expression levels compared with control mice. Treatment with transforming growth factor beta1, which regulates pituitary cell proliferation, reduced Gal-3 as well as p27 expression levels in cultured HP75 pituitary cells and Gal-3 in cultured pituitary cells from p27-null mice, suggesting that p27 is not necessary for the inhibitory effects of transforming growth factor beta1 on the cell cycle in the pituitary. The role of Gal-3 in pituitary cell function was examined by RNA interference experiments. Inhibition of Gal-3 gene expression by RNA interference decreased HP75 cell proliferation and increased apoptosis. These results indicate that Gal-3 has an important role in pituitary cell proliferation and tumor progression.
Cancer Res 2003 May 01
PMID:Differential expression of galectin-3 in pituitary tumors. 1272 47

Helicobacter pylori (H. pylori) infection leads to gastroduodenal inflammation, peptic ulceration and gastric carcinoma. H. pylori may induce disease-specific gene expression in gastric epithelial cells. cDNA microarray for 352 cancer-related genes was used to identify the genes altered by H. pylori (cagA positive) in gastric epithelial AGS cells. Expressions of the genes identified on the microarray and other genes closely associated with these genes were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Western blot analysis and cell adhesion assay were performed to confirm the protein levels of the genes and the role of the genes on cell adhesion in H. pylori-infected AGS cells. As a result, the expression of four genes (galectin 1, aldolase A, integrin alpha5, LIM domain only 7 (LMO7)) were up-regulated by H. pylori in AGS cells, determined by cDNA microarray. RT-PCR analysis showed that the genes up-regulated by H. pylori were the genes regulating cell-cell adhesion and cell-extracellular matrix interaction, such as galectin-1 and galectin-3, integrin alpha5, and LIM domain only 7 (LMO7), and cancer-related glycolytic enzyme aldolase A and C. Cell adhesion to extracellular matrix proteins such as poly-L-lysine and fibronectin was mediated by H. pylori-induced expression of integrin alpha5. RT-PCR and Western blot analysis showed that E-cadherin, regulating cell adhesion and contact cell inhibition, was decreased by H. pylori in AGS cells. In conclusion, the increased expression of cell adhesion molecules and decrease in E-cadherin expression by H. pylori might contribute to cell adhesion, invasion and possibly cell proliferation in gastric epithelial cells.
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PMID:Cell adhesion-related gene expression by Helicobacter pylori in gastric epithelial AGS cells. 1275 65

Galectin-3, a beta-galactoside binding lectin, is highly expressed in thyroid carcinomas of follicular cell origin, whereas neither benign thyroid adenomas nor normal thyroid tissues express galectin-3. We previously showed that antisense inhibition of galectin-3 expression markedly reduced the malignant phenotype of thyroid papillary carcinoma cells. In the present study we transfected galectin-3 cDNA into TAD-2 normal thyroid follicular cells. Stable transfectants expressing galectin-3 acquired the phenotype of serum-independent growth, clonogenicity in soft agar, as well as loss of contact inhibition. We also compared the gene expression profile of the galectin-3 transfectants to that of the vehicle control, which revealed that a series of genes were differentially expressed between the two. They include proliferating cell nuclear antigen, replication factor C, and retinoblastoma genes that participate in G1-S transition. These results indicate the transformation of thyroid follicular cells by galectin-3 and possible involvement of galectin-3 in cell cycle.
Cancer Lett 2003 May 30
PMID:Malignant transformation of thyroid follicular cells by galectin-3. 1276 19

Liver-intestine (LI) cadherin represents a novel type of cadherin within the cadherin superfamily, and is distinguished from other cadherins by specific structural and functional features. Among normal tissues, LI-cadherin is known to be expressed in the intestinal mucosa, while its expression in cancerous tissue has not been investigated to date, except in gastric carcinoma. In the present study we investigated LI-cadherin expression immunohistochemically using our newly established monoclonal antibody in a large set (n = 102) of tumor specimens from patients with ductal adenocarcinoma of the pancreas, and correlated the findings with the patients' survival. LI-cadherin expression was seen focally in normal pancreatic ducts. In carcinoma, well-differentiated carcinoma cases strongly expressed LI-cadherin, whereas less differentiated areas and poorly differentiated carcinoma cases expressed less or were negative. Kaplan-Meier analysis for all patients demonstrated that high LI-cadherin expression (>25% of cells stained positive) correlated with good survival (P < 0.001). Cox regression analyses demonstrated that LI-cadherin expression was one of the strongest predictors of outcome, independent of all other variables, and low LI-cadherin expression correlated with tumor de-differentiation and advanced stage. Furthermore, galectin-3 was identified as being coimmunoprecipitated with LI-cadherin and this interaction was inhibited by lactose in a dose-dependent manner, but not by sucrose. Because galectin-3 has been observed to show a similar expression pattern to LI-cadherin in ductal adenocarcinoma of the pancreas, expression of LI-cadherin and this interaction could have some role in ductal adenocarcinoma of the pancreas.
Cancer Sci 2003 May
PMID:Expression of liver-intestine cadherin and its possible interaction with galectin-3 in ductal adenocarcinoma of the pancreas. 1282 88

The two major theories of cancer metastasis, the seed and soil hypothesis and the mechanical trapping theory, view tumor cell adhesion to blood vessel endothelia and cancer cell aggregation as corresponding key components of the metastatic process. Here, we demonstrate in vitro, ex vivo, and in vivo that metastatic breast and prostate carcinoma cells form multicellular homotypic aggregates at the sites of their primary attachment to the endothelium. Our results suggest that metastatic cell heterotypic adhesion to the microvascular endothelium and homotypic aggregation represent two coordinated subsequent steps of the metastatic cascade mediated largely by similar molecular mechanisms, specifically by interactions of tumor-associated Thomsen-Friedenreich glycoantigen with the beta-galactoside-binding protein, galectin-3. In addition to inhibiting neoplastic cell adhesion to the endothelium and homotypic aggregation, disrupting this line of intercellular communication using synthetic Thomsen-Friedenreich antigen masking and Thomsen-Friedenreich antigen mimicking compounds greatly affects cancer cell clonogenic survival and growth as well. Thus, beta-galactoside-mediated intravascular heterotypic and homotypic tumor cell adhesive interactions at the sites of a primary attachment to the microvascular endothelium could play an important role during early stages of hematogenous cancer metastasis.
Cancer Res 2003 Jul 01
PMID:Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium. 1283 77

Galectin-3 is an endogenous galactose-binding protein that is expressed in several normal and neoplastic tissues and is thought to play a role in a variety of biological processes. In this study we have examined the immunohistochemical expression pattern of galectin-3 in the most representative categories of soft tissue tumors consisting of 162 patients' specimens. Lesions were classified according to histogenetic criteria into 13 major categories. Overall, there were 18 fibrous tumors (13 benign, 4 intermediate and 1 malignant), 21 fibrohistiocytic tumors (5 benign, 11 intermediate and 5 malignant), 22 lipomatous tumors (14 benign and 8 malignant), 20 smooth muscle tumors (12 benign, 5 intermediate and 3 malignant), 2 skeletal muscle tumors (2 malignant), 19 vascular tumors (9 benign and 10 malignant), 6 perivascular tumors (5 benign and 1 malignant), 7 synovial tumors (4 benign and 3 malignant), 3 benign mesothelial tumors, 27 neural tumors (25 benign and 2 malignant), 7 cartilaginous and osseous tumors (4 benign and 3 malignant), 8 miscellaneous tumors and 2 high grade unclassified sarcomas. Galectin-3 was constantly expressed by almost all the major categories of benign, pseudosarcomatous and malignant soft tissue tumors. At this time no data are available in the literature about the expression of galectin-3 distribution in a wide range of soft tissue tumors. In the present work we discuss the significance and the possible usefulness of such findings.
J Exp Clin Cancer Res 2003 Jun
PMID:Evaluation of galectin-3 expression by sarcomas, pseudosarcomatous and benign lesions of the soft tissues. Preliminary results of an immunohistochemical study. 1286 76

We measured the relative expression levels of galectin-3 mRNA to beta-actin mRNA in normal thyroid tissues, thyroid tumor tissues and thyroid-derived fibroblasts. Galectin-3 mRNA was expressed ubiquitously in both benign and malignant thyroid tumors. Although a significant increase in its expression was observed in papillary carcinomas, no significant difference was observed between follicular carcinomas and adenomas. In contrast to the previous optimistic reports using immunohistochemical analysis of the galectin-3 protein expression, these results demonstrate that galectin-3 mRNA may not be a suitable target for molecular-based diagnosis of thyroid carcinomas.
Cancer Lett 2003 Sep 10
PMID:Ubiquitous expression of galectin-3 mRNA in benign and malignant thyroid tumors. 1296 25

The extracellular functions of galectin-7 (p53-induced gene 1) are largely unknown. On the surface of neuroblastoma cells (SK-N-MC), the increased GM1 density, a result of upregulated ganglioside sialidase activity, is a key factor for the switch from proliferation to differentiation. We show by solid-phase and cell assays that the sugar chain of this ganglioside is a ligand for galectin-7. In serum-supplemented proliferation assays, galectin-7 reduced neuroblastoma cell growth without the appearance of features characteristic for classical apoptosis. The presence of galectin-3 blocked this effect, which mechanistically resembles that of galectin-1. By virtue of carbohydrate binding, galectin-7 thus exerts neuroblastoma growth control similar to galectin-1 despite their structural differences. In addition to p53-linked proapoptotic activity intracellularly, galectin-7, acting as a lectin on the cell surface, appears to be capable of reducing cancer cell proliferation in susceptible systems.
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PMID:Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells. 1367 66


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