Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence exists for expression of estrogen receptor beta (ERbeta) in human colonic mucosa. Here we investigated the expression of the classical ER (ERalpha) and of four isoforms of the human ERbeta in HCT116, HCT8, DLD-1, and LoVo colon adenocarcinoma cell lines. In addition, [(3)H]17beta-estradiol (17betaE(2)) binding to intact colon cancer cells was evaluated. RT-PCR and Western blot analyses showed lack of expression of the classical ERalpha in the four colon cancer cell lines. Conversely, wild-type ERbeta isoform 1 was highly expressed in HCT8, HCT116, DLD-1, and LoVo cells and isoforms ERbeta2-5 were present in HCT8 and HCT116 cells. Scatchard and Hill analysis of [(3)H]17betaE(2) binding to the four different colon cancer cells revealed the presence of two classes of binding sites, one with high affinity (K(d) values of 1-2 nM) and the other with lower affinity (K(d) values of 10-20 nM). Forty-eight hour-pretreatment of cells with 1 and 10 nM 17betaE(2) did not induce an increase of progesterone-specific binding to HCT8 cells, while a significant induction was observed after treatment with 10 nM 17betaE(2) in HCT116 and DLD-1 cells and with both concentrations in LoVo cells. In addition, 1 pM-0.1 nM 17betaE(2) significantly induced cell proliferation of HCT8 cells, while reducing growth of HCT116 and DLD1 cells at 10 nM-1 microM concentrations and of LoVo cells at all tested concentrations (1 pM-1 microM). These in vitro findings pose the basis for in vivo functions of ERbeta and ERbeta-interacting molecules in human colon cancer tissue.
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PMID:Functional estrogen receptor beta in colon cancer cells. 1042 18

Epidemiological data suggest a protective effect for estrogen replacement therapy on colon cancer. The estrogen receptor (ER) is required for the action of estrogen. The ER-beta isoform is functionally similar to ER-alpha but has a distinct pattern of expression and transcriptional response to selective estrogen response modulators. Our goal was to investigate the presence of ER-alpha and ER-beta in normal and malignant colon tissue. Human colon cancer tissue and adjacent normal colon tissue were harvested from five male and six female patients undergoing segmental colon resection for colon cancer. Western blot analysis revealed very low levels of ER-alpha protein in tumor and normal colon tissue. In both male and female patients, malignant colon tissue showed a selective loss of ER-beta protein expression when compared to normal colon tissue in the same patient. Semiquantitative reverse transcription-PCR revealed no difference in ER-beta mRNA levels between normal and malignant colon tissue. Malignant transformation of the colon is associated with a marked diminution of ER-beta protein expression, possibly through a posttranscriptional mechanism.
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PMID:Selective loss of estrogen receptor beta in malignant human colon. 1066 68

Knowledge regarding the expression of the recently cloned estrogen receptor beta (ERbeta) in colonic mucosa is limited. In this study, we demonstrated that five human colon cancer cell lines, HT29, Colo320, Lovo, SW480, and HCT116, expressed ERbeta mRNA, but lacked ERalpha mRNA. Results from a cell growth assay demonstrated that these colon cancer cells were not influenced by estrogen, while genistein possessed slight growth inhibitory effects on HT29, Colo320 and Lovo cells at 10 microM, at which concentration is stimulated the growth of ERalpha-positive human breast cancer MCF-7 cells. Tamoxifen inhibited the growth of HT29 and Colo320 cells, dose-dependently, as well as MCF-7 cells. A transfected reporter plasmid containing a vitellogenin estrogen response element could be activated by estradiol in Colo320 cells. Taken together with previous reports, these data suggest that ERalpha and ERbeta may have different biological functions in colon cells.
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PMID:Estrogen receptor beta mRNA in colon cancer cells: growth effects of estrogen and genistein. 1075 41

Estrogen receptor beta (ERbeta) mediated system was tested in three colon cancer cell lines with different sensitivities. These cell lines express ERbeta and androgen receptor (AR) but not the classic estrogen receptor ERalpha. Combinations of ERbeta ligands such as estradiol (E(2)), 17 epiestriol (17E(3)), quercetin (Q) with tamoxifen (TMX) showed marked growth inhibition. The IC(50) were: 2. 0+/-0.3x10(-15), 3.0+/-1.3x10(-10) and 1.2+/-0.5x10(-14) M for DLD-1, DLD-1/5FU and DLD-1/FdUrd, respectively (TMX+E(2) treatment, mean+/-SD, n=3). The IC(50) of TMX+17E(3) were 3.5+/-1.8x10(-8), 2. 6+/-0.9x10(-8) and 1.4+/-1.1x10(-14) M and that of TMX+Q treatment were 3.4+/-2.1x10(-9), 3.6+/-0.2x10(-9) and 2.6+/-1.1x10(-9) M, respectively. This inhibition was significantly different from single agent treatment at the probability level of P<0.002. Thymidylate synthase expression and survivin expression were also markedly inhibited. The inhibition was highest with TMX+Q and lowest with TMX+dehydroepiandrosterone (DHEA). The expression of telomerase was also inhibited by TMX but combination with ERbeta agonists reversed the inhibition. The cellular sensitivity to 5FU was increased: TMX+E(2), TMX+17E(3) and TMX+Q were 1.7+/-0.5x10(-5), 8. 4+/-3.2x10(-8), 8.2+/-2.9x10(-8) and 6.3+/-3.3x10(-8) M for DLD-1 cells and 7.7+/-4.8x10(-5), 9.1+/-4.9x10(-7), 1.5+/-0.3x10(-9) and 5. 7+/-2.2x10(-8) M for DLD-1/5FU. DLD-1/FdUrd cells had IC(50) of 8. 5+/-6.1x10(-5), 1.8+/-0.8x10(-8), 37+/-1.1x10(-9) and 1.6+/-1. lx10(-9) M (mean+/-SD) for the control, TMX+E(2), TMX+17E(3) and TMX+Q. The present data indicate that ERbeta ligands in combination with TMX may have tumor static effects on colon cancer cells.
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PMID:Tamoxifen and gonadal steroids inhibit colon cancer growth in association with inhibition of thymidylate synthase, survivin and telomerase expression through estrogen receptor beta mediated system. 1107 14

Estrogen receptor beta (ER-beta) has recently been detected in a human colon cancer cell line. The aim of this work was to determine whether ER-beta is expressed in human colorectal carcinoma (CRC) tissue and the extent of this expression. ER-beta expression in CRC was investigated by immunohistochemical staining of sections of formalin-fixed, paraffin-embedded tissue from 55 CRC. The percent of positive cells was recorded. ER-beta immunoreactivity was always present in normal epithelium and adenomas in the same sections of some CRC and was always nuclear. In CRC, nuclear ER-beta immunoreactivity was detected in >10% of the cancer cells in 67% of the cases and was almost always associated with cytoplasmic immunoreactivity. There were no statistically significant differences between the ER-beta-positive and -negative groups in regard to depth of invasion, nodal metastases, or survival, regardless of the cut-off value used. We conclude that (1) a significant number of CRCs are positive for ER-beta. (2) estrogen may play an important role in the proliferation of normal colonic epithelium, and (3) there is differential localization of ER-beta immunoreactivity between normal colon, adenomas, and CRCs. Whether different ER-beta isoforms are differentially expressed in CRCs, and whether human CRCs respond to treatment with antiestrogens, is the subject of studies currently in progress.
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PMID:Estrogen receptor beta is expressed in human colorectal adenocarcinoma. 1156 23

The 17HSDs are a group of isozymes that catalyze the interconversion between high-activity 17 beta-hydroxysteroids and low-activity 17-ketosteroids. In the present study, we characterized the expression of 17HSD types 1 and 2 in normal and malignant gastrointestinal tissues and cells. Using the colon as a model for cancer of the gastrointestinal tract, expression of the 17HSD enzymes in cancer development was studied and correlated with proliferation and differentiation markers as assessed by Ki67 and mucin staining, respectively. In normal colon and small intestine, 17HSD type 2 mRNA was expressed in the surface epithelial cells and, to a lesser extent, in the cryptal epithelial cells. In colon-cancer specimens, 17HSD type 2 expression was downregulated both in the tissues and in the cell lines and correlated inversely with the proliferation marker. No expression for the 17HSD type 1 enzyme was observed in normal or cancerous gastrointestinal tract tissues. In line with the expression studies, 17HSD activity measurements with colon cells showed that only the oxidative conversion of E2 to E1 was present, and Northern blot analysis showed the signal only for 17HSD type 2. Localization of the ERs alpha and beta, assessed by immunohistochemistry and in situ hybridization, showed the presence of ER beta in the lamina propria of the colon. Our study shows that 17HSD type 2 expression is associated with the functional integrity of the gastrointestinal tract. The decrease in expression of the type 2 enzyme may increase estrogen influence in colon cancer.
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PMID:Downregulation of estrogen-metabolizing 17 beta-hydroxysteroid dehydrogenase type 2 expression correlates inversely with Ki67 proliferation marker in colon-cancer development. 1177 36

In recent years, several lines of epidemiologic, clinical and experimental evidences have been reported showing that estrogen hormones may be involved in malignant colorectal tumors. The sex differences in site-specific incidence, the increased incidence of colonic cancer in women with breast cancer, the protective effect of increasing parity and the reduced risk among women taking postmenopausal hormones, are all elements suggesting that sex hormones may play a role. Male rats experimentally exposed to the carcinogen dimethylhydrazine, have twice the risk of developing colon cancer and significantly shorter survival times than their female counterparts. Along with the clinical, experimental and epidemiologic findings there are also biologic reasons why estrogen may be protective. Most estrogen action appears to be exerted via the estrogen receptors (ERs) on target cells. ERs have been reported in several solid tumors including gastrointestinal neoplasms such as esophageal, gallbladder, gastric and colorectal cancer. At the end of 1995, a second ER (ER-beta) was cloned from the rat prostate cDNA library and subsequently, the human and mouse homologs. Its demonstration in normal and neoplastic human colorectal tissues and "in vitro" in colonic epithelial cells, has renewed interest in investigating the existence of two ER subtypes. The presence of two ERs could explain the selective actions of estrogens on different target tissues and, particularly, on the gastrointestinal tract. Finally, our studies suggest that estrogens and their receptors play an important role in the growth and progression of colorectal tumors, by interacting with other molecules required for cell proliferation like growth factors and polyamines.
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PMID:Estrogens and colorectal cancer. 1247 78

The discovery of the second estrogen receptor (ER) in 1995 surprised many endocrinologists and resulted in some scepticism regarding its physiological importance. However, 8 years later, it is clear that the multiple actions of estrogen in the body are mediated by two receptors that, although similar, are distinct gene products with non-overlapping functions. This clear delineation of the functions of the two receptors in such a short time was made possible by the development of ER alpha and ER beta knockout mice. The distinct patterns of tissue distribution of these two receptors has heightened interest in novel estrogen targets in the body and has led to awareness of new sites for pharmacological intervention in diseases such as depression, prostate dysfunction, leukaemia, inflammatory bowel disease and colon cancer.
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PMID:What pharmacologists can learn from recent advances in estrogen signalling. 1296 73

Epidemiologic studies reported that the prevalence of hereditary non-polyposis colon cancer (HNPCC) in male is about 1.5-fold higher than that in female. Decreases in circulatory estradiol (E2) have been reported to downregulate the expression of E2 receptor (ER) and significantly increase the risk of colorectal cancer. Patients that received E2 replacement therapy were found to have a reduction in the incidence of colon adenoma and carcinoma. Furthermore, significant decreases in the expression of ER have been found in colorectal cancer specimens. These data strongly suggest the protective roles of E2 and ER against colorectal cancer. However, the mechanisms remain unexplored. LoVo cells were transient transfected to overexpress ER-beta, DNA fragmentation and caspase activity assay were performed to evaluate apoptotic effects. Western blotting was used to evaluate protein levels, and luciferase activity assay to measure the TNF-alpha promoter activity. Our data clearly demonstrated that E2 and ER-beta alone could upregulate p21 and p27 proteins, which further activate caspase-8 and caspase-9 to induce apoptosis in LoVo cell, and the ER-beta. effects were enhanced by E2. However, overexpressed ER-beta did not influence the expression and promoter activity of TNF-alpha. In addition, E2 and overexpressed ER-beta downregulated the beta-catenin proteins which cause the downregulation of its target genes, cyclin D1 and Rb, to inhibit the cell cycle and cell proliferation. The results indicate that overexpressed ER-beta may induce LoVo cell apoptosis and anti-proliferation by increasing p53 signaling in a ligand-dependent manner, and without hTNF-alpha involvement. Efforts aiming at enhancing ER-beta expression and/or activity may prove to be an attractive alternative therapy against colorectal cancer.
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PMID:Apoptotic effects of over-expressed estrogen receptor-beta on LoVo colon cancer cell is mediated by p53 signalings in a ligand-dependent manner. 1683 Jul 93

The soy isoflavone genistein can affect cell metabolism by specifically inhibiting protein tyrosine kinase (PTK) and/or interacting with the estrogen receptors (ERs). Glycosaminoglycans (GAG)/proteoglycans (PG) may participate in tumor development and progression. The synthesis of GAG by two human colon cancer cell lines, HT-29 and SW-1116, and the effects of genistein on their production and distribution between culture medium and cell membrane were studied. The mitogenic activity of genistein on both cell lines growth was also examined. Metabolic labeling, sensitive high pressure liquid chromatography (HPLC) techniques and fluorometric cell proliferation assays were utilized. The results demonstrate that both estrogen receptor beta-positive (ERbeta+) cancer cell lines produced hyaluronan (HA), both extracellular and membrane-associated galactosaminoglycans (GalAG) and heparan sulfate (HS), with the HT-29 cells producing all GAG fractions at significantly higher rates. The observed dose-dependent inhibitory effect of genistein on the synthesis of both secreted and cell-associated GAG/PG by the SW-1116 cells, as well as on their growth, was suggestive of a PTK mechanism. On the other hand, the synthesis of GAGs/PGs by HT-29 cells in the presence of genistein was dependent on their type and localization which implies the active participation of the ERs, which was further supported by the observed growth stimulation at low concentrations of genistein.
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PMID:Protein tyrosine kinase and estrogen receptor-dependent pathways regulate the synthesis and distribution of glycosaminoglycans/proteoglycans produced by two human colon cancer cell lines. 1822 78


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