Browsing by Subject "Tumor suppressor"
Now showing 1 - 6 of 6
Results Per Page
Sort Options
- PublicationOpen AccessA toolbox of lectins for translating the sugar code: the galectin network in phylogenesis and tumors(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Kaltner, Herbert; Gabius, Hans-JoachimLectin histochemistry has revealed cell-type-selective glycosylation. It is under dynamic and spatially controlled regulation. Since their chemical properties allow carbohydrates to reach unsurpassed structural diversity in oligomers, they are ideal for high density information coding. Consequently, the concept of the sugar code assigns a functional dimension to the glycans of cellular glycoconjugates. Indeed, multifarious cell processes depend on specific recognition of glycans by their receptors (lectins), which translate the sugar-encoded information into effects. Duplication of ancestral genes and the following divergence of sequences account for the evolutionary dynamics in lectin families. Differences in gene number can even appear among closely related species. The adhesion/growth-regulatory galectins are selected as an instructive example to trace the phylogenetic diversification in several animals, most of them popular models in developmental and tumor biology. Chicken galectins are identified as a low-level-complexity set, thus singled out for further detailed analysis. The various operative means for establishing protein diversity among the chicken galectins are delineated, and individual characteristics in expression profiles discerned. To apply this galectin-fingerprinting approach in histopathology has potential for refining differential diagnosis and for obtaining prognostic assessments. On the grounds of in vitro work with tumor cells a strategically orchestrated co-regulation of galectin expression with presentation of cognate glycans is detected. This coordination epitomizes the far-reaching physiological significance of sugar coding
- PublicationOpen AccessFrequent intra-tumoural heterogeneity of promoter hypermethylation in malignant melanoma(Murcia : F. Hernández, 2007) Rastetter, M.; Schagdarsurengin, U.; Lahtz, C.; Fiedler, E.; Marsch, V.Ch.; Dammann, R.; Helmbold, P.To investigate intra-tumoural coexistence and heterogeneity of aberrant promoter hypermethylation of different tumour suppressor genes in melanoma, we analyzed the intra-tumoural distribution of promoter methylation of RASSF1A, p16, DAPK, MGMT, and Rb in 339 assays of 34 tumours (15 melanoma primaries, 19 metastases) by methylation-specific PCR, correlation to histopathology and RASSF1A expression. We detected promoter hypermethylation of at least one gene in 74% of tumours (30%, 52%, 33%, 20%, and 40% for RASSF1A, p16, DAPK, MGMT and Rb, respectively). 70% of the cases exhibited an inhomogeneous methylation pattern (17%, 45%, 33%, 20%, and 40% for RASSF1A, p16, DAPK, MGMT and Rb, respectively). Samples from the core of the tumours represented the methylation state of the whole tumours more accurately than the periphery. Local intra-tumoural correlation was found between the promoter hypermethylation state of p16 and Rb or p16 and DAPK, or epitheloid tumour cell type and RASSF1A or p16 methylation. Mitosis rate and sex was correlated with methylation of RASSF1A. Histological results confirmed that promoter hypermethylation of RASSF1A led to aberrant expression patterns. We conclude that intra-tumoural inhomogeneity of promoter hypermethylation is frequent in melanoma and this supports the hypothesis of clonal instability during progression of melanomas. In prognosis studies, missing the intra-tumoural sample representativeness may result in a reduction of the sensitivities or specificities.
- PublicationOpen AccessHtrA1 loss is related to aggressive behavior parameters in sentinel node positive breast cancer(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Franco, Renato; Collina, Francesca; Di Bonito, Maurizio; Botti, Gerardo; Montanaro, Donatella; Di Maio, Luigi; Vincenz, Bruno; Landi, Gabriella; D’Aiuto, Massimiliano; Caraglia, Michele; Baldi, AlfonsoAim: HtrA1, a member of the High Temperature Requirement Factor A family of oxidative stress-response proteases seems to play a role as a tumor suppressor, being down-regulated in a series of human cancers during their progression. Particularly, low HtrA1 mRNA levels have been observed in breast cancer patients with more aggressive clinical features. These have been shown to relate to a longer disease free and overall survival, with more pronounced effects in axillary nodes positive patients. Subjects and Methods: We have analyzed for immunohistochemical HtrA1 expression a series of 66 sentinel node positive breast cancers through Tissue Micro Array technology. Results: HtrA1 was absent to low in 29 cases, medium in 19 cases and high in 18 cases. Our data revealed a positive significant relation between HtrA1 expression level and estrogen (p=0,002) and progestinic receptor expression (p=0.003) and a negative correlation with histological grading (p=0.028), proliferation index (p=0.05), common BC histotypes (p=0.040), luminal A and B subtypes (p=0.001), metastasis development (p<0.0001) and local relapse (p<0.0001). Finally, no correlation was recorded between HtrA1 expression level and breast cancer histology type and metastasis to non sentinel nodes. Interestingly HtrA1 loss in SLN metastasis was able to predict positive non sentinel nodes (p=0.001). Conclusions: Low HtrA1 expression is significantly related to breast cancer poor prognosis parameters, and HtrA1 loss in sentinel nodes is related to metastasis of non sentinel nodes, offering a further marker useful for BC prognostic stratification.
- PublicationOpen AccessMolecular pathology of head and neck cancer(Murcia : F. Hernández, 2002) Crowe, D.L.; Hacia, J.G.; Hsieh, C.L.; Sinha, U.K.; Rice, D.H.Squamous cell carcinoma of the head and neck region (HNSCC) is the sixth most frequent cancer worldwide, comprising almost 50% of all malignancies in some developing nations. In the United States, 30,000 new cases and 8,000 deaths are reported each year. Survival rates vary depending on tobacco and alcohol consumption, age, gender, ethnic background, and geographic area. This variability reflects the multifactorial pathogenesis of the disease. Early detection and diagnosis has increased survival but the overall 5 year rate of 50% is among the lowest of the major cancers. Differences between normal epithelium and cancer cells of the upper aerodigestive tract arise from specific alterations in genes controlling DNA repair, proliferation, immortalization, apoptosis, invasion, and angiogenesis. These proteins include both tumor suppressors and activating oncogenes which regulate a wide variety of intracellular signaling pathways. Included in these pathways are growth factor receptors, signal transducers, and transcription factors which regulate DNA damage response, cell cycle arrest, and programmed cell death. In head and neck cancer, alterations of three signaling pathways occur with sufficient frequency and produce such dramatic phenotypic changes as to be considered the critical transforming events of the disease. These changes include mutation of the p53 tumor suppressor, inactivation of the cyclin dependent kinase inhibitor p16, and overexpression of epidermal growth factor receptor (EGFR). This review will focus on the molecular changes which occur in these pathways and how they contribute to the pathogenesis of HNSCC.
- PublicationOpen AccessSOX7: From a developmental regulator to an emerging tumor suppressor(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Stoval, Daniel B.; Cao, Paul; Sui, GuangchaoSOX7 belongs to the SOX (SRY-related HMG-box) family of transcription factors that have been shown to regulate multiple biological processes, such as hematopoiesis, vasculogenesis and cardiogenesis during embryonic development. Recent studies indicate that several SOX family members play important roles in tumorigenesis. In this review, we introduce SOX7 gene and protein structures, and discuss its expression and functional role in cancer development and progression. SOX7 is frequently downregulated in many human cancers and its reduced expression correlates with poor prognoses of several cancers. Functional studies reveal many tumor suppressive properties of SOX7 in prostate, colon, lung, and breast cancers. To date, although a few target genes of SOX7 have been identified, SOX7-mediated gene expression has not been investigated in a cancer-relevant context. Our recent studies not only for the first time demonstrate a tumor suppressive role of SOX7 in a xenograft mouse model, but also unravel that many genes regulating cell death, growth and apoptosis are affected by SOX7, strongly supporting a pivotal role of SOX7 in tumorigenesis. Thus, currently available data clearly indicate a tumor suppressive role of SOX7, but the mechanisms underlying its gene expression and tumor suppressive activity remain undetermined. The research of SOX7 in cancers remains a fertile area to be explored. Histol Histopathol 29, 439-445 (2014)
- PublicationOpen AccessThe versatile functions of the transcriptional coactivators p300 and CBP and their roles in disease(Murcia : F. Hernández, 2002) Janknecht, R.p300 and CBP are highly homologous c o a c t ivators which promote gene transcription by bridging between DNA-binding transcription factors and the basal transcription machinery, by providing a s c a ffold for integrating transcription factors, and by modifying transcription factors and chromatin through acetylation. The p300/CBP cofactors are invo l ved in a plethora of physiological processes, and their activity is essential for embryogenesis. Chromosomal translocations affecting the p300 and Cbp genes are the cause of hematological malignancies, and C b p haploinsufficiency is a hallmark of the Rubinstein-Taybi syndrome. In addition, mutations in the C b p or p 3 0 0 gene, accompanied by loss of the other allele, have been found in various kinds of tumors. Furthermore, inhibition of CBP and p300 function in n e u r o d eg e n e r a t ive diseases caused by polyglutamine expansion may be an underlying cause for cytotoxicity. Approaches to modulate p300/CBP function may be instrumental in the development of novel therapies directed against viral infections, cancer and neurodegenerative diseases.