Disease relevance of LGALS7

• Here, we provide evidence indicating that galectin-7 functions as an important molecule in the dissemination of lymphoma cells in vivo [1].
• For example, up-regulation of galectin-7 is associated with rat mammary carcinomas and with progression to T-cell malignancy [1].
• We also found that inhibition of galectin-7 in aggressive lymphoma cells correlated with a decreased invasion of tumor cells in target organs and a reduced expression of matrix metalloproteinase-9, a gene associated with a poor prognosis in non-Hodgkin's lymphoma [1].
• Galectin-7 is a beta-galactoside binding protein specifically expressed in stratified epithelia and notably in epidermis, but barely detectable in epidermal tumors and absent from squamous carcinoma cell lines [2].
• In serum-supplemented proliferation assays, galectin-7 reduced neuroblastoma cell growth without the appearance of features characteristic for classical apoptosis [3].

High impact information on LGALS7

• These functions of TIGAR correlated with an ability to protect cells from ROS-associated apoptosis, and consequently, knockdown of endogenous TIGAR expression sensitized cells to p53-induced death [4].
• DRAM, a p53-induced modulator of autophagy, is critical for apoptosis [5].
• We further show that RAD001 sensitizes cells to cisplatin by inhibiting p53-induced p21 expression [6].
• Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis [7].
• The p53-induced genes p21 and 14-3-3sigma are each required for the G(2) arrest and allow a specific test of this fundamental tenet [8].

Chemical compound and disease context of LGALS7

• Using a tetracycline-regulated p53 expression system and cDNA library subtraction procedure, we identified several p53-induced gene transcripts in human Saos-2 osteosarcoma cells that are novel on the basis of their size, regulation, and low abundance [9].
• Although normal cells and wild-type p53-expressing tumor cells showed similar responses to actinomycin D and camptothecin treatment, the transcriptional activity of stabilized p53 induced by deferoxamine mesylate, which mimics hypoxia, in normal cells was lost in all three tumor cell lines tested [10].
• 5-aza-2'-deoxycytidine upregulates caspase-9 expression cooperating with p53-induced apoptosis in human lung cancer cells [11].
• The enhanced resistance of the co-cultured SH-SY5Y cells to the toxicity of 6-hydroxydopamine is attributed to the ability of astrocytes to prevent the increase of p53 induced by this toxin [12].
• Different levels of p53 induced either apoptosis or cell cycle arrest in a doxycycline-regulated hepatocellular carcinoma cell line in vitro [13].

Biological context of LGALS7

• We found that stable transfection of lymphoma cells with a plasmid encoding antisense galectin-7 cDNA significantly inhibited the dissemination and invasion of lymphoma cells to peripheral organs, thereby increasing the survival of mice [1].
• A model for p53-induced apoptosis [14].
• Because p53 transcriptional activity is increased by genotoxic stresses we have examined the possible effects of ultraviolet radiations (UVB) on galectin-7 expression in epidermal keratinocytes [2].
• Cloning, expression, and chromosome mapping of human galectin-7 [15].
• 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 [3].

Anatomical context of LGALS7

• We finally examined the expression of galectin-7 in 50 specimens of different mature B-cell neoplasms and found high galectin-7 expression levels in a significant proportion of mature B-cell neoplasms but not in normal B cells [1].
• On the other hand, as the mRNA levels for galectins-3 and -7 are notably upregulated at culture confluence (galectin-7) or at postconfluence (galectin-3), their expression is thought to be related to the differentiated state of keratinocytes [16].
• Immunoblotting as well as immunofluorescence analysis of human tissues with a specific galectin-7 antibody revealed a narrow distribution of the protein which was found mainly in stratified squamous epithelium [15].
• The protein encoded by the galectin-7 clone comigrated with IEF 17 as determined by two-dimensional (two-dimensional gel electrophoresis) analysis of proteins expressed by transiently transfected COS-1 cells, and bound lactose [15].
• Galectin-7 as a potential mediator of corneal epithelial cell migration [17].

Associations of LGALS7 with chemical compounds

• Further analyses of actinomycin D-induced apoptosis demonstrated that galectin-7 expression causes enhanced caspase-3 activity and poly(ADP-ribose) polymerase cleavage, and the potentiation of apoptosis by galectin-7 was completely abrogated by a caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone [18].
• Galectin-7, a human 14-kDa S-lectin, specifically expressed in keratinocytes and sensitive to retinoic acid [19].
• The stimulatory effect of galectin-7 on corneal epithelial wound closure was specifically inhibited by a competing sugar, beta-lactose, but not by an irrelevant disaccharide, sucrose [17].
• The results directly implicate proline oxidase and the proline/P5C pathway in p53-induced growth suppression and apoptosis [20].
• Expression of p73 resulted in a reduction of the ectopically expressed p53 in transient transfections or of the endogenous p53 induced by Adriamycin- or UV-mediated damage [21].

Physical interactions of LGALS7

• The p53-induced apoptosis was abrogated by NS5A and the inhibition effect correlates well with the binding ability of NS5A to p53 [22].
• The ability of ATF3 to stabilize p53-induced pathways thus represents a means of effectively countering DNA damage caused by environmental insult the latter leading to oncogene activation and ultimately malignant transformation [23].

Regulatory relationships of LGALS7

• By virtue of carbohydrate binding, galectin-7 thus exerts neuroblastoma growth control similar to galectin-1 despite their structural differences [3].
• ASPP proteins interact with p53 and specifically enhance p53-induced apoptosis but not cell cycle arrest [24].
• Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage [25].
• UV but not gamma irradiation accelerates p53-induced apoptosis of teratocarcinoma cells by repressing MDM2 transcription [26].
• MDMX stability is regulated by p53-induced caspase cleavage in NIH3T3 mouse fibroblasts [27].

Other interactions of LGALS7

• This protein was recently found to be highly inducible by p53 in a colon carcinoma cell line, DLD-1, and designated as PIG1 (for p53-induced gene 1) [18].
• Therefore, galectin-7 is a pro-apoptotic protein that functions intracellularly upstream of JNK activation and cytochrome c release [18].
• Among the five gallinacin genes evaluated, the Gal3 and Gal7 SNPs in broiler sires were found to be associated with antibody production after S. enterica serovar Enteritidis vaccination [28].
• RESULTS: High levels of galectin 7 expression were associated with rapid recurrence rates and dismal prognoses in these 81 stage IV hypopharyngeal SCCs, a feature not observed with galectin 3 and one observed weakly, if at all, with galectin 1 [29].
• Transfection of a galectin-7 expression vector results in a significant increase in terminal deoxynucleotidyltransferase-mediated UTP end labeling-positive keratinocytes [2].

Analytical, diagnostic and therapeutic context of LGALS7

• DNA microarray analysis revealed genes that are differentially expressed between galectin-7 and control transfectants [18].
• Here we report the cloning and expression of a novel member of this family (galectin-7) that correspond to IEF (isoelectric focusing) 17 (12,700 Da; pI, 7.6) in the human keratinocyte protein data base, and that is strikingly down-regulated in SV40 transformed keratinocytes (K14) [15].
• CONCLUSIONS: These data suggest that the immunohistochemical determination of galectin 7 expression in the case of high-risk hypopharyngeal cancers is a meaningful tool to identify patients who should benefit from aggressive postsurgical adjuvant therapy after surgery, including not only radiotherapy, but also chemotherapy [29].
• At the end of the healing period, expression levels of galectin-7 messenger RNA and protein were analyzed using semiquantitative reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemical localization studies [17].
• The distribution of galectin-7 mRNAs and protein was studied by in situ hybridization and immunolabelling of various human, rat and mouse epithelia [30].

References