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| Predmet: Indeed, this data showed that activation of CD40 in presence of CD3 CD28 CpG re Po jún 30, 2014 9:24 am | |
| Amplification is one of the activating mechanisms of proto oncogenes during carcinogenesis. Among the frequently buy JNJ-7706621 amplified regions in human malignancies, amplifications of 11q13 were found in breast cancers, esophageal squamous cell carcinoma, and head and neck cancers. In this region, several genes were located and the amplified region encompassed more than one of the tested loci. In addition, region q13 of chromosome 11 was pointed out to have a high pene trance gene for breast cancer in the study of 19 non BRCA1 2 families. However, amplification does not necessarily result in increased expression of the affected gene. Taking into account that gene products rather than the genes themselves are effector molecules controlling biological behavior of the cells, we need to know the ex pression changes of the genes located in 11q13 and their clinical significance to understand their contribution to tumor cell behavior.<br><br> Among the genes located in the region of 11q13, FADD was reported as a driver in the 11q13 amplicon in laryngeal pharyngeal cancer. FADD is an adaptor molecule interacting with many kinds of death purchase LDN193189 receptors and induces apoptosis by caspase 8. FADD ex pression was associated with metastasis in squamous cell carcinoma of the head and neck and poor prognosis in oral squamous cell carcinoma and lung adenocar cinoma. Because the amplification of FADD does not confined in a single gene, TMEM16A or PPFIA1, which are in close proximity to FADD, may be ampli fied concomitantly. In addition, the BAC clone, which is used as a template when synthesizing the fluorescence in situ hybridization probe for FADD, includes the regions of TMEM16A and PPFIA1.<br><br> Confirmation of amplification by FISH cannot differenti ate copy number alterations among the genes. The locus encompassing these three genes is amplified LY2228820 in several malignancies, including breast cancer. TMEM16A is associated with activation of the calcium dependent chloride channel and regulates cell proliferation. TMEM16A is considered to be proto oncogenic and increases tumor growth when overexpressed in gastro intestinal stromal tumors, and head and neck cancer. Previous reports claimed that the calcium chloride channel influenced the growth of tumors and loss of TMEM16A, leading to decrease in tumor size. However, the mechanism of tumor growth by TMEM16A overexpression is not known.<br><br> PPFIA1 is a member of the LAR protein tyrosine phosphatase interacting protein family. PPFIA1 is amp lified in human breast cancers and promotes inva siveness of breast and cervical cancer cells. Also, PPFIA1 acts as a tumor suppressor and regulates cell motility by interacting with ING4. When expres sion of PPFIA1 was reduced, invasiveness of head and neck squamous cell carcinomas was found to increase. Although TMEM16A, FADD and PPFIA1 are co amplified in many malignancies, the combined effect of the three gene expressions has not been evaluated to date. To understand the net effect of these three gene alterations, we screened the gene expressions by immunohistochemistry and analyzed the association with clinicopathological pa rameters, including disease free survival. | |
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