Disease relevance of C8orf4

• Thus, LSM1, BAG4, and C8orf4 are breast cancer oncogenes that can work in combination to influence the transformed phenotype in human mammary epithelial cells [1].
• Moreover, C8orf4 is expressed in most normal colon mucosa samples, and is not expressed in most colon cancer metastases or colon cancer cell lines [2].
• C8orf4 is a transforming growth factor B induced transcript downregulated in metastatic colon cancer [2].
• 2. The overexpression of TC-1 in papillary carcinoma suggests that it may have an important role in thyroid carcinogenesis [3].
• NIS plays key roles in thyroid pathophysiology as the route by which iodide reaches the gland for thyroid hormone biosynthesis and as a means for diagnostic scintigraphic imaging and for radioiodide therapy in hyperthyroidism and thyroid cancer [4].

Psychiatry related information on C8orf4

• The differences seen between these and other published results may be related to differences in radiation doses to the thyroid, latency period between time of radiation exposure and development of clinically apparent thyroid cancer, and ethnic background of the study populations [5].
• Age at which smoking commenced, duration of smoking, number of cigarettes smoked per day, pack-years of smoking and alcohol consumption were not associated with altered thyroid cancer risk [6].
• Our findings suggest that thyroid cancer prevention via dietary modification of soy and/or phytoestrogen intake in other forms may be possible but warrants further research at this time [7].
• These findings suggest that LCs may play an important role in the immunologic defense mechanisms of the host against the tumor only in the papillary type of thyroid cancer [8].
• CONCLUSIONS: These results provide some initial support for the hypothesis that physical activity may reduce risk of thyroid cancer [9].

High impact information on C8orf4

• Translation of cumulative thyroid dose attributable to 131I to predictions of increased rates of thyroid cancer appears problematic and is the subject of further study [10].
• Epidemiology of thyroid cancer [11].
• METHODS: One hundred twenty-seven patients with thyroid cancer underwent whole-body radioiodine scanning by two techniques: first after receiving two doses of thyrotropin while thyroid hormone therapy was continued, and second after the withdrawal of thyroid hormone therapy [12].
• Prolonged follow-up confirms an elevated risk of thyroid cancer and Graves' disease as well as hypothyroidism in these patients [13].
• The molecular biology of Laron dwarfism and medullary thyroid cancer [14].

Chemical compound and disease context of C8orf4

• We have studied the incidence of leukaemia among 46,988 Swedish patients exposed to iodine-131 (131I) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer [15].
• To determine the validity of this presumption we have estimated--by applying modifications of the life-table method--the clinical and screening age-at-diagnosis distributions for MEN-2, using families from the Cancer Research Campaign Medullary Thyroid Cancer Register and one large American family [16].
• Effects of vinblastine and 5-fluorouracil on human glioma and thyroid cancer cell monolayers and spheroids [17].
• Breast cancer in women diagnosed at or after age 65 was also associated with fasting blood glucose >/=7.0 mmol/l. Positive associations with glucose values >5.3 mmol/l were noted for thyroid cancer, gallbladder/bile duct cancer and multiple myeloma in men and women combined [18].
• OBJECTIVE: To assess the long-term efficacy of radiofrequency ablation (RFA) and percutaneous ethanol (EtOH) injection treatment of local recurrence or focal distant metastases of well-differentiated thyroid cancer (WTC) [19].

Biological context of C8orf4

• We further showed that three of these genes (LSM1, BAG4, and C8orf4) induce transformed phenotypes when overexpressed in MCF-10A cells, and overexpression of these genes in combination influences the growth factor independence phenotype and the ability of the cells to grow under anchorage-independent conditions [1].
• C8orf4 is a gene regulated by TGF beta signaling and loss in advanced colon cancer suggests C8orf4 may play a role in colon cell differentiation or growth regulation [2].
• Using fluorescence in situ hybridization, TC-1 was localized to chromosome 8p11 [3].
• Ubiquitously expressed in human tissues, the TC-1 sequence showed no homology to any known gene, but matched a cluster of ESTs [3].
• In the patients with medullary thyroid cancer, radial bone-density values were normal (-0.26 +/- 0.39), but spinal density was significantly reduced (-0.75 +/- 0.17, P less than 0.01) [20].

Anatomical context of C8orf4

• Colon cancer primary tumors showed reduced expression of C8orf4 relative to normal mucosa, possibly reflecting contributions of C8orf4 expression in stromal cells [2].
• These results suggest that overexpression of TC-1 may be important in thyroid carcinogenesis [21].
• Although the mortality rate from thyroid cancer is low, it is the highest among cancers affecting the endocrine glands (excluding the ovary) [22].
• The risk was increased significantly for acute myeloid leukemia (standardized incidence ratio [SIR] 52.3), non-Hodgkin lymphoma (SIR 8.3), parotid gland tumors (SIR 33.4), thyroid cancer (SIR 13.3), brain tumors (SIR 10.1), and soft tissue sarcoma (SIR 9.1) [23].
• PATIENTS AND METHODS: Parenchymal function was assessed by quantitative salivary gland scintigraphy performed prospectively in 50 patients with differentiated thyroid cancer before and 3 months after HD-RIT with either 3 GBq iodine ((131)I) (n=21) or 6 GBq (131)I (n=29) in a double-blind, placebo-controlled study [24].

Associations of C8orf4 with chemical compounds

• We show that the protein can be phosphorylated by cyclic AMP-dependent protein kinase and protein kinase C, and the activity of both of these kinases is up-regulated when cells are stably transfected with TC-1 [21].
• BACKGROUND: To detect recurrent disease in patients who have had differentiated thyroid cancer, periodic withdrawal of thyroid hormone therapy may be required to raise serum thyrotropin concentrations to stimulate thyroid tissue so that radioiodine (iodine-131) scanning can be performed [12].
• Thyroid hormone treatment had no effect on the rate of thyroid cancer [25].
• [18F]Fluorodeoxyglucose PET is also useful in some endocrine tumors, particularly in recurrent or metastatic thyroid cancer where the degree of accumulation of the radionuclide has prognostic value [26].
• METHODS: The Swedish Cancer Registry and the Uppsala-Orebro Regional Cancer Registry were used to identify persons with papillary or follicular thyroid cancer diagnosed from January 1, 1980, through December 31, 1992, among residents of the Uppsala Health Care Region [27].

Physical interactions of C8orf4

• BACKGROUND: Sodium/iodide symporter (NIS) is a key protein in iodide transport by thyroid cells and this activity is a prerequisite for effective radioiodide treatment of thyroid cancer [28].

Regulatory relationships of C8orf4

• TC1 (C8orf4) enhances the Wnt/beta-catenin pathway by relieving antagonistic activity of Chibby [29].
• These analyses highlighted C8orf4 as induced by TGF beta in colon cells [2].
• PTEN expression is reduced in a subset of sporadic thyroid carcinomas: evidence that PTEN-growth suppressing activity in thyroid cancer cells mediated by p27kip1 [30].
• Because thyroid cancer cells express functional TSH receptors (TSHR), TSHR-mRNA in peripheral blood might serve as a tissue-/cancer-specific marker [31].
• We hypothesized that signaling via the epidermal growth factor receptor (EGFR) stimulates thyroid cancer cell invasion by altering the expression and cleavage of matrix metalloproteinases (MMPs) [32].

Other interactions of C8orf4

• TC1 interacts with Chibby (Cby) and thereby enhances the signaling pathway by relieving the antagonistic function of Cby on the beta-catenin-mediated transcription [29].
• Our data suggest that activating BRAF mutations may be an important event in the development of papillary thyroid cancer [33].
• Transient ectopic expression of PTEN in thyroid cancer cell lines induces cell cycle arrest and cell type-dependent cell death [34].
• Exposure to neutralizing antibodies against IL-4 and IL-10 resulted in down-modulation of Bcl-2 and Bcl-xL, death of a considerable percentage of thyroid cancer cells, and sensitization of the residual tumor population to cytotoxic drug-induced apoptosis [35].
• Thus, IL-4 and IL-10 may represent key targets for the treatment of thyroid cancer [36].

Analytical, diagnostic and therapeutic context of C8orf4

• Overexpression of TC-1 in thyroid cancer was confirmed in 15/16 paired samples by RT-PCR and Northern analysis [3].
• Fifty patients received 131I treatment for ablation of residual thyroid tissue after surgical thyroidectomy, and 26 had 131I treatment for metastatic thyroid cancer [37].
• In contrast, however, large epidemiological studies of areas of endemic goiter do not show an association of human thyroid cancer with iodine deficiency and presumed chronic thyroid gland stimulation [38].
• Radioimmunoassays measure serum levels of TG, and these levels are abnormally elevated in patients with metastatic thyroid cancer [39].
• A population-based case-control study of thyroid cancer [40].

References