Analysis of high-risk prostate cancer (PC) families with at least one confirmed case of primary brain cancer (BC) has identified a region of genetic linkage on chromosome 1p36 termed CAPB.
Collectively, these results show that MAPK pathways ERK, JNK/SAPK, and P38-MAPK represent a significant component in the regulation of u-PA expression in human CaP.
Early linkage results have provided targeted candidate regions for prostate cancer susceptibility loci, including HPC1 on chromosome 1q23-25, PCAP on chromosome 1q42-43, CAPB on chromosome 1p36, linkage to chromosome 8p22-23, HPC2 on chromosome 17p, HPC20 on chromosome 20q13, and HPCX on chromosome Xq27-28.
In total, 126 individuals (including 89 men with prostate cancer) were genotyped using markers that map to five prostate cancer susceptibility loci, namely HPC1 at 1q24-25, PCAP at 1q42.2-43, CAPB at 1p36, HPC20 on chromosome 20, and HPCX at Xq27-28.
Taken together with studies indicating that EphB2 may have an essential role in cell migration and maintenance of normal tissue architecture, our findings suggest that mutational inactivation of EPHB2 may be important in the progression and metastasis of prostate cancer.
Inhibition of TGF-β in an TRAMP-C2 CaP model in C57BL/6 mice using 1D11 was associated with downregulation of DNMTs and p-ERK and impairment in tumor growth.
In conclusion, our findings have identified critical molecular mechanisms involving ERK-mediated ERG activation that could be exploited for therapeutic intervention in ERG-positive prostate cancers.
With inhibition of p38, ERK, and JNK, the TSP-2-induced cell migration and MMP-2 expression were abolished, indicating that the TSP-2's effect on PCa is MAPK dependent.
Here we have analyzed the EPHB2 gene for germline alterations in 101 individuals either with 1) CRC and a personal or family history of prostate cancer (PC), or 2) intestinal hyperplastic polyposis (HPP), a condition associated with malignant degeneration such as serrated adenoma and CRC.
Our findings indicate that loss of function of DUSP22 in PCa cells leads to aberrant activation of both EGFR-ERKs and AR signaling and ultimately progression of PCa, supporting the potential for novel therapeutic design of harnessing DUSP22 in the treatment of PCa.-Lin, H.-P., Ho, H.-M., Chang, C.-W., Yeh, S.-D., Su, Y.-W., Tan, T.-H., Lin, W.-J.
Our findings indicate that oncogenic ETS rearrangements cause a cell migration gene expression program to switch from RAS/ERK control to PI3K/AKT control and provide a possible explanation for the high frequency of PTEN, but not RAS/RAF mutations in prostate cancer.
We have found that the nuclear ERK-selective phosphatase DUSP5 is downregulated in colorectal tumours and cell lines, as previously observed in gastric and prostate cancer.