Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This investigation aimed to identify patterns of copy number change in colorectal tumor progression from adenoma to liver metastasis. Fifty-three microdissected sub-regions from 17 cases of colorectal cancer were assigned to one of six histopathologically defined categories: coexisting adenoma, tumor above the muscularis layer, tumor within the muscularis layer, tumor extending through the bowel wall to serosal fat, lymph node metastasis, and liver metastasis. Microdissected samples were treated by a microwave processing step and then used as templates for universal PCR amplification. PCR products were fluorophore labeled and subjected to comparative genomic hybridization. Copy number changes were found in all samples, and every chromosome arm (excluding acrocentric short arms) was affected. More losses than gains were detected, but there were no significant differences between the numbers of changes seen in each category. Each individual sample revealed unique changes, additional to those shared within each case. The most frequently observed gains were of X and 12q. The most common losses were of 8p, 16p, 9p, 15q, 18q, and 10q. Nominally significant associations were observed between metastatic tumor and loss of 12q24.1 or 10p13-14, non-metastatic tumor and loss of 8q24.1, tumor extending to serosal fat and loss of 6q24-25 or gain of 4q11-13, tumor extending to serosal fat and metastatic lesions and loss of 4q32-34 or 22q11-12, and adenoma and loss of 15q24. Loss of 4q32-34 remained highly significant after correction for multiple testing. Adenoma was the only category not to show loss of 17p. These data reveal a genetically heterogeneous picture of tumor progression, with a small number of changes associated with advanced disease.
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PMID:Analysis of colorectal tumor progression by microdissection and comparative genomic hybridization. 1280 Jan 48

Cyclooxygenase-2 and prostaglandin E(2) (PGE(2)) levels are increased in colorectal cancers and a subset of adenomas. PGE(2) signaling through the EP4 receptor has previously been associated with colorectal tumorigenesis. However, changes in EP4 expression during adenoma to carcinoma progression have not been investigated, neither has whether levels of EP4 influence important markers of malignant potential, such as anchorage-independent growth or the tumors growth response to PGE(2). We report using immunohistochemistry that in vivo EP4 receptor protein expression was increased in colorectal cancers (100%) as well as adenomas (36%) when compared with normal colonic epithelium. EP4 expression was also higher in colorectal carcinoma compared with adenoma cell lines and increased with in vitro models of tumor progression. Adenoma (PC/AA/C1 and RG/C2) and carcinoma cell lines (HT29) were growth stimulated by PGE(2) up to 0.5 micromol/L. However, although carcinoma and transformed adenoma (PC/AA/C1SB10C, a transformed derivative of PC/AA/C1) cells remain stimulated by higher doses of PGE(2) (10 micromol/L), the adenoma cell lines were inhibited. Interestingly, enforced expression of EP4 in the adenoma cell line, RG/C2, resulted in stimulation of growth by 10 micromol/L PGE(2) and promoted anchorage-independent growth. Both in vivo and in vitro data from this study suggest that increased EP4 receptor expression is important during colorectal carcinogenesis. We propose that high levels of PGE(2) in a tumor microenvironment would select for cells with increased EP4 expression, and that the EP4 receptor may therefore represent an important target for colorectal cancer prevention and treatment.
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PMID:Increased EP4 receptor expression in colorectal cancer progression promotes cell growth and anchorage independence. 1654 Jun 60