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Thyroid stimulating hormone (TSH) is known to increase intracytoplasmic cyclic adenosine monophosphate (cAMP) and to regulate the growth of normal follicular cells. The aim of this study was to explore the role of the cAMP-mediated signaling pathway stimulated by TSH as a cell growth modulator in human thyroid cancer cells. One papillary thyroid cancer cell line, K1 cells and two anaplastic thyroid cancer cell lines, TTA1 and TTA2 cells were treated with forskolin, which directly activates adenyl cyclase to raise the level of intracellular cAMP. Forskolin suppressed thyroid cancer cell proliferations, especially in K1 cells, in a dose-dependent manner and induced growth arrest at the G0/G1 phase of the cell cycle. We also examined the expression of mitogen activated protein kinase (MAPK) after the forskolin treatment. Forskolin reduced the activation of growth factor induced MAPK activity. In conclusion, we demonstrated that forskolin was involved in G1 arrest and MAPK activation in K1 thyroid cancer cells. Our study suggests that the TSH signal mediated by cAMP acts as a negative regulator in thyroid cancer cells, unlike that in normal follicular cells.

Renal cell carcinoma (RCC) shows various clinical behaviors, and currently surgical modalities are the only effective therapy against this cancer. To discern the genomic background affecting clinical characteristics such as metastasis, we analyzed the gene expression profiles of the RCCs by DNA microarray using cell lines originating from primary or metastatic lesions. RNA was extracted from ten SKRC RCC cell lines and gene expression profiling was performed using a cDNA microarray of nearly 4,000 human cDNA clones. We compared the gene expression profiles between these SKRC cell lines and the normal renal proximal tubular cell line and among SKRC cell lines that showed different characteristics. The clustering of the selected 62 genes revealed similar profiling patterns between SKRC-17 and SKRC-29 cells that were derived from metastatic RCC lesions. Another cell line from a metastatic lesion, SKRC-52, with a unique spindle-shaped morphology, had a different pattern of expression profiling from the other cell lines. We found several genes up-regulated in the cell lines from metastatic lesions; transgelin, which is reportedly involved in cell proliferation and migration, was up-regulated in SKRC-52. The unique profiling pattern of gene expression clearly correlated with cell morphology and metastatic potential. Such profiling might contribute to identifying the genes involved in the clinical characteristics of RCC.

The molecular background of sporadic endometrial cancer coexisting with colorectal or breast cancer is not clear. We investigated microsatellite instability (MSI) and status of mismatch repair (MMR) gene product, MLH1, MSH2 and MSH6, in 63 sporadic endometrial cancers coexisting with colorectal or breast cancer. Sixteen sporadic endometrial cancers with colorectal cancers (EC), 26 sporadic endometrial cancers with breast cancer (EB) and 21 endometrial cancers without a coexisting cancer (control) were analyzed. EC had the highest frequency of MSI among the 3 groups (EC, 69%; EB, 23%; and control, 43%). Incidence of low-frequency MSI was significantly higher in EC (38%). Among endometrial cancer cases diagnosed before age 50, all high-frequency MSI (MSI-H) cases belonged to EC. Interestingly, incidence of MSI-H was significantly higher in tamoxifen-non-treated cases (75%) than that of treated cases (14%). These results suggest that alterations in MMR genes appear to be involved in carcinogenesis of EC but seem to be uncommon in those of EB. Presence of MSI in sporadic endometrial cancer may be a useful marker to predict the risk of colorectal cancer.

Chromosomal gains of 1q21-q22 and 13q12-q14 were closely related with the chemoresistance of patients with ovarian cancer in our previous CGH (comparative genomic hybridization) study. We conducted the present study to determine the amplified genes on chromosome 1q. Comparisons of relative copy numbers of clinically platinum-sensitive ovarian tumors (CR-group, n=14) and platinum-resistant tumors (PD-group, n=14) were carried out using real-time PCR from ten different gene loci on chromosome 1q. Increased copy numbers were frequently observed in PD-group tumors, especially in the region between WI-8123 and MUC1. Relative copy number of MUC1 over 1.5 was observed in 13 (92%) of 14 PD-group tumors and 3 (21%) of 14 CR-group tumors (p