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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined expression of E-cadherin cell-cell adhesion molecule, which is supposed to have invasion-suppressing activity, in 53 cases with endometrial carcinoma. Fresh frozen sections were immunostained with a mouse monoclonal antibody to human E-cadherin (HECD-1). E-cadherin expression was inversely correlated with grade of tumor (p = 0.0267), depth of myometrial invasion (p = 0.0146) and pelvic and paraaortic node metastases (p = 0.0184 and p = 0.0419, respectively). Multivariate analysis revealed that among histologic grade, nuclear grade, and E-cadherin expression, E-cadherin expression was most strongly correlated with depth of myometrial invasion (p = 0.0491). These results suggest that decreased expression of E-cadherin facilitates invasion of endometrial carcinoma.
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PMID:[Abnormal E-cadherin expression as a risk factor for deep myometrial invasion and lymph node metastasis in endometrial carcinoma]. 762 96

The in vitro invasive ability, the expression of cell adhesion molecule E-cadherin, activity of matrix metalloproteinase (MMP) and K-ras point mutation were investigated in eight human endometrial carcinoma cell lines. 1) In vitro invasive abilities of endometrial carcinoma cell lines depend on the degree of cell differentiation and the origin of cell lines. A poorly-differentiated carcinoma cell line (NUE-1) and a cell line derived from metastatic lymph node (SNG-M) were more invasive than moderately-(HEC-1A, HEC-1BE) and well-differentiated (HEC-6, Ishikawa) cell lines. 2) Immunohistochemically, less or non-invasive cell lines expressed E-cadherin strongly, whereas a highly invasive cell line (NUE-1) expressed E-cadherin weakly. 3) When cultured on Matrigel-coated dishes, the tumor cells derived from moderately- and well-differentiated carcinoma aggregated with each other and did not invade Matrigel in the invasion assay. The aggregated cells expressed E-cadherin more strongly when cultured on Matrigel. 4) 72-kD gelatinase (MMP-2) was secreted in serum-free conditioned medium of all cell lines. In an invasive cell line (NUE-1,SNG-M), the activity of MMP-2 was stronger than in other cell lines. And the activity of 92-kDa gelatinase (MMP-9) was detected in most invasive cell line (NUE-1). 5) Point mutation of K-ras codon 12 was detected in four of eight (50%) cell lines by the PCR-RFLP method. The changes in the DNA sequence were identified, but K-ras point mutation was not correlated with in vitro invasiveness of the tumor cells.
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PMID:[The factors involved in invasive ability of endometrial carcinoma cells]. 804 Jun 23

Decreased E-cadherin expression in tumor cells has been suggested to promote tumor invasiveness. We examined E-cadherin expression in 30 cases of endometrial carcinoma by immunohistochemistry using a monoclonal antibody to E-cadherin and investigated its correlation with other histopathologic features of the tumor. We observed that: (1) E-cadherin expression decreased with loss of differentiation (P < 0.05); (2) E-cadherin expression was inversely correlated with depth of myometrial invasion (P < 0.05); (3) decreased E-cadherin expression was correlated with paraaortic node metastasis (P < 0.01); and (4) multivariate analysis comparing the depth of myometrial invasion to the pattern of E-cadherin expression, histologic grade, nuclear grade, and lymph-vascular space invasion showed that the depth of myometrial invasion was most strongly correlated with decreased E-cadherin expression (P < 0.005). These findings seem to be consistent with the concept that the dissociation of cancer cells due to decreased expression of E-cadherin facilitates invasion of tumor cells.
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PMID:Decreased E-cadherin expression in endometrial carcinoma is associated with tumor dedifferentiation and deep myometrial invasion. 818 77

The first step of invasion and metastasis is the detachment of cancer cells in the primary tumor, which is mainly controlled by the function in the adherens junction, consisting of E-cadherin associated proteins (E-cadherin, alpha- and beta-catenins, vinculin, alpha-actinin, and actin). The cell-to-cell aggregation activity and the expressions of E-cadherin, and alpha- and beta-catenin mRNAs in Ishikawa cells of well-differentiated endometrial cancer were significantly suppressed by estrogen. These suppressions were reversed by progesterone, medroxyprogesterone acetate (MPA) and danazol. Proteins in the adherens junction appeared to be expressed intact and to be functional in Ishikawa cells. Persistent estrogen predominant milieu might contribute to the detachment of well-differentiated endometrial cancer cells, leading to spreading of those cells, while progestins and danazol protect estrogen-induced spreading of those cells.
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PMID:Progestins and danazol effect on cell-to-cell adhesion, and E-cadherin and alpha- and beta-catenin mRNA expressions. 863 63

The development and growth of gynecological cancers are related to steroid hormone actions. Alternatively, this prompts us to study biological contribution of sex steroids for invasion and metastasis in gynecological cancers. The first step of metastasis is the detachment of tumor cells. The adherens junction forms a main cell-to-cell junctional complex, mainly consisting of E-cadherin, alpha- and beta-catenins, etc. Estrogen suppressed the expression of their mRNAs, and the adhesive function of cells via adherens junction in endometrial cancer cells. Progestin and danazol reversed the estrogen-induced suppression. Estrogen enhanced invasiveness of endometrial cancer cells though the reconstituted basement membrane and interstitium using the Boyden chamber. Progestin reduced the estrogen-induced invasiveness. The final step of metastasis is tumor-derived neovascularization for growth of metastatic cancer cells. Progestin inhibited basic fibroblast growth factor (FGF) activity, which mainly contribute to tumor-derived neovascularization, regardless of growth-inhibition in some endometrial cancers. Progestin inhibits basic FGF in well-differentiated (WD) endometrial cancer cells, but not in poorly differentiated (PD) endometrial cancer cells. TNP470, a inhibitor of vessel endothelial proliferation, inhibited directly basic FGF in the PD. Therefore, the adequate combination therapy of progestin and TNP470 could efficiently inhibit angiogenic potential of heterologous endometrial cancers. The ratio of estrogen receptor exon 5 splicing variant (ER delta E5) to wild type-ER mRNA expression increased in some metastatic lesions of cancers. The dominant expression of ER delta E5 mRNA might be related to metastatic potential of gynecological cancers. Progesterone receptor from A (PR-A), initiated from in-frame AUG present in the PR from B (PR-B) mRNA, lacks the N-terminal 164 amino acids of PR-B, and acts as a progestin-dependent, trans-dominant repressor of PR-B function and other steroid receptor function. The expression of PR-B mRNA was dominantly expressed in all metastatic gynecological cancers given. This might be related to metastatic potential of gynecological cancers. To know tumorigenic potential of sex steroid receptors, ER, PR-A and PR-B genes were transfected to NIH3T3 cells. Transfected cells with PR-A gene alone formed a few colonies in double soft agar. On the other hand, the cells with PR-B and ER genes under the presence of estradiol formed plenty of colonies. Therefore, overexpression of PR-B under the absence of PR-A might be related to tumorigenic potential. In conclusion, estrogen could enhance some steps of metastasis in endometrial cancers, and progestin could inhibit the estrogen-induced events, regardless of growth-inhibition. Relative over-expression of ER exon 5 splicing variant, and PR-B might contribute to metastatic potential in gynecological cancers.
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PMID:[Endocrinological contribution for invasion and metastasis in gynecological cancers]. 880 31

The enhancement of the in vitro invasive ability and the morphological changes caused by anti-E-cadherin antibody HECD-1 were investigated by in vitro invasion assay and electron microscopy in three human endometrial carcinoma cell lines. The cell lines were NUE-1 (E-cadherin negative and high in vitro invasive ability), HEC-1BE and HEC-108 (E-cadherin positive and low in vitro invasive ability). In NUE-1 invasive ability was not enhanced by HECD-1, but in HEC-1BE and HEC-108 invasive ability was enhanced to 223 +/- 41.2% and 307 +/- 173% by 5 micrograms/ml HECD-1. Morphologically NUE-1 invaded the extracellular matrix (Matrigel) with a long micro villis. But in HEC-1BE and HEC-108 the villis did not invade the Matrigel, the whole cell invaded it. Together with HECD-1, HEC-1BE and HEC-108 were changed to become similar to the NUE-1 cell line with high invasive ability and the micro villis invaded the Matrigel.
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PMID:[Experimental studies on the cell adhesion molecule E-cadherin and in vitro invasion of endometrial carcinoma cell lines]. 884 59

We have previously shown that the connexin (Cx) 26 and 32 genes are expressed during the secretory phase of the human endometrium and that their expression is downregulated during the proliferative phase, suggesting a role for intercellular transduction in cell growth control in human endometrium. To further study the possible role of cell-to-cell interaction in growth regulation, we immunohistochemically analyzed 80 endometrial samples (30 of normal endometrium, 20 of endometrial hyperplasia, and 30 of endometrial cancer) for the expression of E-cadherin; alpha-, beta-, and gamma-catenin; adenomatous polyposis coli (APC) protein, and sex-steroid hormone receptors at three points in the cells: the cell-to-cell border, the cytoplasm, and the nucleus. In this study, moderate or strong staining of beta-catenin in the nuclei was observed in 60.0% of endometrial hyperplasia samples and 30.0% of endometrial cancer samples, although the beta-catenin gene was mutated in only two of the nine samples that showed the intensive nuclear staining. Western blotting analysis showed that the samples that had intense nuclear staining of beta-catenin had much higher expression of beta-catenin than the samples that did not have nuclear staining. Furthermore, normal endometrium showed nuclear localization, especially in the mid- and late-proliferative and early-secreting phases of the menstrual cycle. The results suggest that the nuclear localization of beta-catenin observed in endometrial hyperplasia and endometrial cancer, as in other tumors, implies that beta-catenin/Wnt-1 signal transduction is highly activated in carcinogenesis of the endometrium as well as in normal physiological conditions.
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PMID:Nuclear localization of beta-catenin in normal and carcinogenic endometrium. 1041 Nov 47

Seventeen patients with endometrial cancer were studied. Tissues of primary (P) and metastatic (M) lesions were obtained from 8 patients and complete sets of P, M and Recurrent (R) lesions were obtained from 9 patients during a follow-up period of 1-10 years. Expressions of estrogen receptors, progesterone receptors, multidrug resistance protein-1, multidrug resistance-related protein, c-erbB-2, membrane-type metalloproteinase, human telomerase RNA, human telomerase reverse transcriptase RNA, E-cadherin and autocrine motility factor receptor were studied by RT-PCR. Also, telomeric restriction fragment length (TRFL) and microsatellite instability were determined between P, M and R. The results indicate that there are significant differences in the gene expression frequency during tumor progression. The mismatch rate ranged from 0 to 47.1% between P and M and from 14.3% to 66.7% between P and R, respectively. The TRFL analysis showed a marked reduction in P and M (P vs. M: 8.2 +/- 0.9 vs. 5.6 +/- 0.4 kb, mean +/-SEM, n = 9, p = 0.002 by paired Student's t test). The length further decreased in R (P vs. R: 8.2 +/- 0.9 vs. 3.2 +/- 0.7, p = 0.01, M vs. R: 5.6 +/- 0.4 vs. 3.2 +/- 0.7, p = 0.005). The genomic instability/replication error was tested by AluI arbitrary primed polymerase chain reaction (AP-PCR). Five out of 17 patients showed an altered replication error pattern (29.4%). The mean number of abnormal AluI AP-PCR patterns in M and R compared to the P was 1.5 (M) and 4 (R). The difference between the P and R was statistically significant (p < 0.04). The present data indicate that biological behavior of cancer cells in P, M and R may differ significantly.
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PMID:Gene expression in primary, metastatic and recurrent lesions of endometrial cancer. 1054 51

Since its discovery as a protein associated with the cytoplasmic region of E-cadherin, beta-catenin has been shown to perform two apparently unrelated functions: it has a crucial role in cell-cell adhesion in addition to a signaling role as a component of the Wnt/wg pathway. Wnt/wg signaling results in beta-catenin accumulation and transcriptional activation of specific target genes during development. It is now apparent that deregulation of beta-catenin signaling is an important event in the genesis of a number of malignancies, such as colon cancer, melanoma, hepatocellular carcinoma, ovarian cancer, endometrial cancer, medulloblastoma pilomatricomas, and prostate cancer. beta-catenin mutations appear to be a crucial step in the progression of a subset of these cancers, suggesting an important role in the control of cellular proliferation or cell death. The APC/beta-catenin pathway is highly regulated and includes players such as GSK3-beta, CBP, Groucho, Axin, Conductin, and TCF. c-MYC and cyclin D1 were recently identified as a key transcriptional targets of this pathway and additional targets are likely to emerge. Published 1999 John Wiley & Sons, Inc.
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PMID:beta-catenin signaling and cancer. 1058 Sep 87

The effect of conophylline, a new vinca alkaloid that inhibits ras expression, on tumour cell adhesion and infiltration was evaluated using a human endometrial cancer cell line. When SNG-II, a highly differentiated human endometrial cancer cell line, was exposed to conophylline, the cells developed filamentous processes at concentrations which did not affect cell proliferation (0.03-0.3 microgram/ml). After exposure to conophylline (0.3 microgram/ml), cells adherent to matrigel- and type IV collagen-coated wells respectively decreased to 26.9% and 33.3% of the number in the untreated control culture (p < 0.01). In an in vitro invasion assay using a Boyden chamber, infiltration of cells exposed to conophylline decreased to 19.4% (0.3 microgram/ml) (p < 0.01) of the control. In a wound assay, conophylline inhibited the movement of cells at 24 hr after wounding. Flow cytometric analysis revealed that expression of integrin beta 1 was not altered by conophylline, but E-cadherin and CD44 were decreased. The expression of E-cadherin and CD44 could be changed by conophlline.
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PMID:Inhibition of attachment and chemotactic invasion of uterine endometrial cancer cells by a new vinca alkaloid, conophylline. 1065 93


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