We describe here the de®nition and characterization of antigen CT-8/HOM-TES-85 encoded by a previously unknown gene and identi®ed by serological expression screening using antibodies from a seminoma patient. Intriguingly, the leucine zipper region of CT-8/HOM-TES-85 shows an atypical amphipathy with clusters of hydrophobic residues that is exclusively shared by the Nmyc proto-oncogene. CT-8/HOM-TES-85 gene is tightly silenced in normal tissues except for testis. However, it is frequently activated in human neoplasms of di erent types including lung cancer, ovarian cancer, melanoma and glioma. Endogenous as well as heterogeneously expressed CT-8/HOM-TES-85 targets predominantly to the nucleus forming a distinctive speckled pattern of nuclear dots arranged in macromolecular structures. By co-localization studies these speckles were identi®ed as loci of transcriptional activity and splicing, suggesting that CT-8/HOM-TES-85 may be involved in these processes. The aberrant expression of CT-8/HOM-TES-85 in human neoplasms might therefore be involved in cancer associated alterations of transcriptional or post-transcriptional processes and thus may disclose new mechanisms involved in the manifestation of the cancer phenotype.
The expression of vitamin D-receptor (VDR) and retinoid X-receptor alpha (RXR-alpha) has been analysed immunohistochemically in benign (n = 62 and n = 5 respectively) and malignant (n = 228 and n = 15 respectively) breast tissue samples using a monoclonal antibody 9A7gamma against VDR and a polyclonal antibody against RXR-alpha. A recently developed immunoreactive scoring method (IRS) was employed. The expression of VDR was detected at the RNA-level using the reverse transcriptase-polymerase chain reaction. A statistically significant higher expression of VDR at the protein level was seen in breast cancer compared with benign breast tissue, whereas at the mRNA level no visible differences in the expression of VDR were found. A higher expression of RXR-alpha was seen in breast cancer compared with benign breast tissue. Our findings indicate that breast tissue may be a new target organ for therapeutically applied vitamin D and retinoid analogues. VDR and RXR-alpha are upregulated at the protein level in breast carcinomas as compared to normal breast tissue, indicating a possibly increased sensitivity to therapeutically applied vitamin D analogues. New vitamin D analogues exerting less calcemic side effects may be promising new drugs for the treatment or chemoprevention of breast carcinomas as well as of precancerous breast lesions. Combination therapies of vitamin D and retinoid analogues with fewer side effects seen promising for the treatment of breast cancer.
We analyzed human Mut-S-Homologon-2 expression in normal endometrial tissue (n = 15) and malignancies of the uterine corpus (n = 40). Human Mut-S-Homologon-2 protein was investigated immunohistochemically on frozen sections, using a highly sensitive streptavidin-peroxidase technique and a specific mouse monoclonal antibody (clone FE11). Human Mut-S-Homologon-2 labeling pattern was compared with the staining pattern of the proliferation marker Ki-67 in the same tumors. A human Mut-S-Homologon-2 immunoreactivity score (human Mut-S-Homologon-2-IRS: negative 0-1; weak 2-3; moderate 4-6; strong 8-12) for semiquantitative analysis of human Mut-S-Homologon-2 expression is presented. In normal endometrial tissue samples we found weak nuclear immunoreactivity for human Mut-S-Homologon-2 in 67%, whereas the remaining 33% were negative for human Mut-S-Homologon-2 (mean human Mut-S-Homologon-2-IRS 1.25 ± 1.29). All malignancies of the uterine corpus analyzed revealed moderate to strong nuclear immunoreactivity (mean human Mut-S-Homologon-2-IRS 9.00, ± 3.16). Human Mut-S-Homologon-2 staining was heterogeneous, with visual differences among individual tumor cells. Expression of human Mut-S-Homologon-2 protein was consistently and strongly upregulated in tumor cells of malignancies of the uterine corpus compared with normal endometrial tissue (human Mut-S-Homologon-2-PP p<0.001; human Mut-S-Homologon-2-IS p<0.001; human Mut-S-Homologon-2-IRS p<0.001). No statistically significant correlation in comparing the labeling patterns for human Mut-S-Homologon-2 with the labeling patterns for Ki-67 (mean percentage of Ki-67-positive tumor cells 22.00% ± 17.20) was observed in malignancies of the uterine corpus (human Mut-S-Homologon-2-PP p=0.443; human Mut-S-Homologon-2-IS p=0.234; human Mut-S-Homologon-2-IRS p=0.173). Our findings indicate that human Mut-S-Homologon-2 is expressed in normal human endometrial tissue and that expression of human Mut-S-Homologon-2 may be of importance for the genetic stability of malignancies of the uterine corpus in vivo.
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