Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:012675 (S100)
 6,012 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical, cytogenetic, histopathologic, and immunohistochemical data were obtained in a series of 11 small round cell tumors (SRCT) of bone and soft tissue with the translocation t(11;22) (q24;q12). Ten cases were primary in bone, and one was of extraskeletal origin. According to conventional histopathologic criteria, 10 cases were Ewing's sarcomas (ES) and one was a peripheral neuroectodermal tumor (PNET). Besides the t(11;22), six cases had additional chromosomal aberrations, including trisomy 7 and partial trisomy for the long arm of chromosome 1, which have both been described as nonspecific secondary abnormalities often associated with tumor progression. The tumors were screened for neural differentiation with an antibody panel consisting of neuron-specific enolase, S100 protein, Leu-7, chromogranin, synaptophysin, and neurofilament. Three cases of ES were positive for S100 protein. The PNET and one case of ES were positive for neuron-specific enolase. All of the remaining immunohistochemical stains were negative. Hence, five of 11 SRCT of bone or soft tissue with the t(11;22) showed morphologic and/or immunohistochemical evidence of neural differentiation. In this limited series of cases, no cytogenetic or prognostic differences could be demonstrated between cases with and without a neural phenotype. Our results support the hypothesis that SRCT of bone of soft tissue with the t(11;22) form a single biologic entity displaying varying degrees of neuroectodermal differentiation. The clinical significance of additional cytogenetic abnormalities and of morphologic or immunohistochemical evidence of neural differentiation in this group of tumors needs to be further studied.
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PMID:Neural differentiation in small round cell tumors of bone and soft tissue with the translocation t(11;22)(q24;q12): an immunohistochemical study of 11 cases. 217 3

The human genome contains large regions that are highly structured. Sequence-related members of multigene families are often found in a clustered organization. Here we describe a previously unrecognized gene cluster composed of genes coding for calcium-binding proteins of the S100 family. The linkage of six S100 genes was established by pulsed-field gel electrophoresis, and a contiguous DNA sequence of 15 kilobases containing the full coding region of four different S100 genes was characterized. This is the tightest mammalian gene cluster discovered so far to our knowledge. Two additional S100 genes are located within the cluster, both of which exhibit unique structural features when compared with other S100 genes. The product of S100E is cysteine-rich, whereas that of S100D contains a long hydrophobic N-terminal tail. The gene cluster was assigned to chromosome 1q21, one of the bands showing rearrangements in neoplasms at high frequency. The deregulated expression of some S100 genes in the cluster during tumor progression suggests that chromosomal abnormalities may influence the expression of S100 genes in late stages of cancer, particularly in association with the formation of metastases.
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PMID:Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E. 834 67

It has been proposed that metastasin 1 (mts1), a member of the S100 Ca(2+)-binding protein family, may play a role in tumor progression and metastasis. In order to test this possibility, we have performed gene transfer experiments using a human sense mts1 expression vector and human MCF7 malignant epithelial cells which do not express endogenous mts1. In vitro, mts1 expression did not modify proliferative or invasive properties of transfected MCF7 cells. In vivo, MCF7 cells expressing mts1 were associated with tumors exhibiting necrosis, and abundant fibrous and poorly cellular stroma. Immunohistochemical staining of endothelial cells showed that, in the presence of mts1, the number and the size of tumoral microvessels were decreased and some of them were collapsed. No metastases were observed in mice with either mts1-expressing or nonexpressing tumors. In summary, these results indicate that (i) in vitro and in vivo, mts1 does not confer invasive properties to MCF7 cells, and (ii) mts1 expression by MCF7 cells leads to defective tumor microvessels, leading to the hypothesis that mts1 may have a negative effect on neoangiogenesis and/or on the maintenance of blood vessels.
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PMID:Defective tumor vascularization induced by metastasin 1 expression. 918 51

CaN19, a member of the S100 family of calcium-binding proteins, is known to be "underexpressed" in cultured breast carcinoma-derived cell lines relative to their normal counterparts. By Northern blotting, we confirm these results and find that CaN19 is also markedly "underexpressed" in several carcinoma-derived cell lines of the skin, oral mucosa, and urogenital tract. However, exceptions to the inverse correlation between CaN19 expression and malignancy have been identified, bringing into question the hypothesis that CaN19 functions as a tumor suppressor gene. Unexpectedly, CaN19 mRNA was strongly expressed in bulk specimens of basal and squamous cell carcinomas of the skin and oral cavity. However, in situ hybridization revealed only limited CaN19 expression in tumor cells themselves; the bulk of expression is localized to hyperplastic perilesional epidermis. Tumor cell expression of CaN19 was similar in primary and locally metastatic tumors, indicating that this gene is not necessarily down-regulated during tumor progression. Coordinate overexpression of CaN19 and the "hyperproliferalive" keratin K6a was observed only in tissues undergoing squamous differentiation. Taken together with other recent results from our laboratory, these findings suggest the hypothesis that CaN19 participates in an epidermal growth factor receptor-dependent pathway of regenerative squamous differentiation.
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PMID:CaN19 expression in benign and malignant hyperplasias of the skin and oral mucosa: evidence for a role in regenerative differentiation. 923 Feb 22

Because telomerase activity is necessary for cell immortality and probably associated with tumor progression, we have evaluated a possible aid for quantitation of the activity to predict intrahepatic recurrences after surgery in patients with hepatocellular carcinoma (HCC). HCC tissues obtained by surgical resection from 20 patients were studied. Telomerase activity was expressed as peaks with a periodicity through a fluorescence-based telomeric repeat amplification protocol using an autosequencer, and the quantity of activity was calculated from peak areas. A ratio of fluorescence intensity depending on telomerase to that of an internal standard was used as a value of relative telomerase activity (RTA). RTA in serially diluted S100 extracts from HepG2 cells was well correlated with the amount of the extracts. The mean RTA value of 36.4 +/- 27.8 (mean +/- SD, 3.21 to 105) in 9 patients suffering from early recurrences after surgery was significantly higher than that (9.84 +/- 7.65; mean +/- SD, 3.00 to 29.0) in 11 patients without intrahepatic recurrences during the early period (P = .004). These results indicate that RTA value can be a useful predictor for intrahepatic recurrences during the early period after surgical resection of HCC.
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PMID:Quantitation of telomerase activity in hepatocellular carcinoma: a possible aid for a prediction of recurrent diseases in the remnant liver. 946 37

Psoriasin (S100A7) is a relatively new member of the S100 gene family that is located within the S100 gene cluster on chromosome 1q21 and shares the typical calcium binding domains that define this family of proteins. It was first identified as a 11.4 kDa cytoplasmic and secreted protein isolated from skin involved by psoriasis, which can be induced in cultured squamous epithelial cells. It is now known to be expressed by both normal cultured and malignant keratinocytes and malignant breast epithelial cells within ductal carcinoma in situ, suggesting an association with abnormal pathways of differentiation. Current evidence supports a role in the pathogenesis of inflammatory skin disease, as a chemotactic factor for hematopoietic cells, and a role in early stages of breast tumor progression in association with the development of the invasive phenotype. While therapeutic potential as a target for modulation of the inflammatory response in psoriasis awaits further studies, potential clinical applications already include a role as a detection marker for squamous cell carcinoma and a diagnostic marker to distinguish in situ from invasive breast cancer cells.
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PMID:Psoriasin (S100A7). 969 57

The S100 family of calcium binding proteins has been shown to be involved in a variety of physiological function, such as cell proliferation, extracellular signal transduction, intercellular adhesion, motility as well as cancer metastasis. The role played by a member of the S100 gene family, viz. S100A4 (also referred to as mtsl, 18A2/mtsl, pEL-98, p9Ka, metastasin) in the control of cell proliferation as well as in cancer invasion and metastasis has now been extensively studied in a number of laboratories. The protein encoded by S100A4 gene is now known to be capable of regulating cell cycle progression, modulating intercellular adhesion and invasive and metastatic properties of cancer cells. The S100A4 protein appears to be able to sequester and disable the p53 suppressor protein which controls G1-S transition of cells as well as the exit of cells from the S phase into mitosis G2-M transition is believed to involve the induction of stathmin (Op18) gene expression. The expression of this gene has been found to parallel that of S100A4, S100A4 also appears to take part in the homeostasis of growth, with apparent involvement also in growth factor signal transduction and apoptotic cell death. There is considerable evidence that S100A4 expression alters the adhesive properties of cells, possibly by remodelling the extracellular matrix and promoting a redeployment of adhesion-mediating macromolecules occurring in the extracellular matrix. Using transfection technology, it has been shown that over-expression of S100A4 enhances lung colonisation by cancer cells. The transfection and expression of antisense constructs, in contrast, inhibit metastatic localisation in the lung. S100 proteins levels in serum and in tumour tissue are increasingly being monitored and have been regarded as good indicators of the state of cancer progression. Valuable evidence has accumulated regarding the expression of S100A4 in human melanomas. In carcinoma of the breast, the level of expression of S100A4 has been found to be closely related to metastatic spread of the cancer to regional lymph nodes. The purpose of this review is to emphasise the need to focus sharply upon the mechanisms by which S100 proteins in general and S100A4 in particular subserve the wide variety of functions currently attributable to them.
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PMID:S100A4 (MTS1) calcium binding protein in cancer growth, invasion and metastasis. 970 88

Adenoid cystic carcinoma (ACC) of the salivary gland is generally an indolent tumor that pursues a protracted clinical course with recurrences and late metastasis. The authors report three cases of ACC with dedifferentiation to high-grade malignant neoplasms. One patient developed dedifferentiated ACC ab initio, with extensive local disease and multiple lymph nodes metastases at first presentation, requiring mutilating surgery. Two patients had dedifferentiated ACC 4 and 10 years, respectively, following excision of the initial uncomplicated ACC; both patients died within 1.5 years after recurrence. Histologically, the dedifferentiated component appeared as a distinct population of anaplastic cells with more abundant cytoplasm, irregular-shaped tumor islands infiltrating a desmoplastic stroma, and total loss of bicellular differentiation characteristic of ACC. The immunophenotypic profile was altered in comparison with the ACC, such as acquisition of strong staining for S100 protein and lack of a myoepithelial component in the two cases that were interpreted as being poorly differentiated adenocarcinoma. One case was a sarcomatoid neoplasm with focal myoepithelial features. Overexpression of p53 protein was demonstrated in the dedifferentiated component in one case, and overexpression of cyclin D1 was seen in two cases. The dedifferentiated component had a higher Ki67 index than did the ACC. To the authors' best knowledge, this report represents the first documentation of dedifferentiation as a form of tumor progression in ACC, which is associated with a sinister clinical outcome.
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PMID:Dedifferentiation in adenoid cystic carcinoma of salivary gland: an uncommon complication associated with an accelerated clinical course. 1102 11

A new transitional cell carcinoma cell line, BCCA-1, derived from a primary urinary bladder carcinoma, was characterized with respect to the growth patterns of in vitro culture, xenotransplantability in SCID mice and immunophenotypic profile. The most unusual finding was a strong tendency of forming many aggregates (multicell spheroids) in the first few days of flask cultures, followed by the attachment of spheroids to monolayer fibroblasts, which came along from stroma of the same tumor. Unlike those reported tumor spheroids whose peripheral layers contained proliferative cells, BCCA-1 spheroids rarely contained mitotic cells. The three-dimensional architecture of BCCA-1 spheroids drastically changed by the attachment of spheroids to fibroblasts, from which epithelial tumor cells spread; this was accompanied by pseudopodia formation and highly aggressive growth of tumor cells. As the fibroblasts degenerated due to overgrowth, tumor cells started to aggregate by retracting their pseudopods and forming many semi-attached spheroids, which eventually detached from the sheet of degenerated fibroblasts. BCCA-1 produced solid tumors as xenografts in SCID mice by subcutaneous injection with as low as 5 x 10(6) cells, suggesting malignant nature of these cells. Immunostaining revealed the expression of MHC-class I, S100 protein, cytokeratin CK7 and CK20, beta-HCG, CEA, epithelial membrane antigen, Le(y) and folate-binding protein by this tumor. While the biological significance of spheroid formation of this kind by BCCA-1 cells remains unclear, it may represent a protection mechanism, by which TCC cells could sustain their viability under unfavorable culture conditions, but proliferate when the conditions became improved, such as the presence of fibroblasts. Our results point to the importance of tumor-associated stromal fibroblasts in TCC tumor progression. Further mechanistic studies to elucidate the mechanism involved in the stromal cell contact mediated-activation of TCC cells in this model system are warranted.
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PMID:Human bladder carcinoma cells with an unusual pattern of in vitro growth: transition from nonproliferative spheroids to active monolayer growth upon interaction with tumor-derived fibroblasts. 1081 Mar 50

The levels of S100 Ca(2+)-binding proteins correlate with the progression of certain tumors, but their role, if any, in carcinogenesis is still poorly understood. S100B protein associates with both the p53 oligomerization domain (residues 325-355) and the extreme C terminus of the tumor suppressor p53 (residues 367-392). Consequently, S100B inhibits p53 tetramer formation and p53 phosphorylation mediated by protein kinase C, on p53 C-terminal end. In this report, we show that the S100B protein decreases p53 DNA binding and transcriptional activity. The effect of S100B is reflected in vivo by a reduced accumulation of p53, p21, and MDM2 protein levels in co-transfection assays and in response to bleomycin. The S100B can still interact with p53 in the absence of p53 extreme C-terminal end and reduce the expression of p53 downstream effector genes. These data indicate that S100B does not require p53 extreme C-terminal end to inhibit p53 activity. Collectively, these findings imply that elevated levels of S100B in tumors such as astrocytomas and gliomas could inhibit p53 functions and contribute to cancer progression.
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PMID:Inhibition of p53 transcriptional activity by the S100B calcium-binding protein. 1145 63


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