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)

Angiogenesis is required during tumor progression. Emerging data, including the presence of estrogen receptors in endothelium, suggests that estrogens can mediate endothelial proliferation and differentiation. Therefore, it is likely that anti-estrogenic drugs can also exert their effects in endothelial cells. The purpose of this work was to evaluate the effect of one anti-estrogenic agent, ICI 182,780, in human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs with 5 different concentrations of ICI 182,780 resulted in decreased cell viability and increase in apoptosis. Gene expression profile of these ICI-treated cells evaluated by cDNA array presented an upregulation of 68 newly expressed genes, whose expression was absent from both control and 17beta-estradiol-treated HUVECs. Most of these genes were implicated in both intrinsic and extrinsic apoptotic pathways. Furthermore, ICI 182,780 incubation prevented HUVECs from formity capillary-like tubules in a Matrigel assay. These findings suggest that besides blocking tumor cell proliferation in an estrogen receptor-dependent manner, ICI 182,780 impaired angiogenesis by preventing branching and capillary-like tubule formation and by activating apoptotic pathways in endothelial cells.
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PMID:Role of the estrogen antagonist ICI 182,780 in vessel assembly and apoptosis of endothelial cells. 1255 34

It has been suggested that circulating soluble Fas (sFas) contributes to tumor progression. However, little is known about the role of sFas in breast cancer. This study was designed with the aim of elucidating the possible relation between sFas and breast cancer. A series of 57 consecutive patients with invasive breast cancer undergoing surgery were prospectively included in the study and evaluated. Venous blood samples were collected before surgery. Sera were obtained by centrifugation and stored at -70 degrees C until assayed. The control group consisted of 12 patients with benign breast tumors (6 with fibrocystic disease, 6 with fibroadenoma). Serum concentrations of sFas were measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor staging, age, estrogen receptor status, lymph node status, tumor grading, and TNM staging were reviewed and recorded. The mean value of circulating sFas in patients with invasive breast cancer was 794.2 +/- 183.0 pg/ml and that of the control group 582.1 +/- 62.8 pg/ml; the difference was significant (p < 0.001). Furthermore, there were significantly higher serum levels of sFas in the older patients (age > or = 50) (p = 0.020) and in those with a more advanced TNM stage (p = 0.021). In the multivariate analysis, TNM stage (p = 0.005) appeared to be an independent factor for significantly higher circulating sFas in patients with invasive breast cancer. Thus circulating sFas levels may reflect the severity of invasive breast cancer. Hence the possible prognostic value of sFas for breast cancer deserves further elucidation and evaluation with long-term patient follow-up.
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PMID:Circulating soluble Fas in patients with breast cancer. 1255 31

We have developed four new mammary adenocarcinoma cell lines from the C3(1)/SV40 Large T-antigen (Tag) transgenic mouse model: M28N2 and M27H4 (weakly tumorigenic), M6 (carcinoma), and M6C (metastatic). The C3(1) promoter directs Tag expression to the mammary epithelium and 100% of female C3(1)/Tag transgenic mice develop mammary adenocarcinoma in a predictable and progressive manner. The cell lines we developed from this model are demonstrated to be of epithelial origin and display growth rates, both in vitro and following subcutaneous inoculation into nude mice, that are consistent with their representative stage of tumor progression. The more tumorigenic cell lines, M6 and M6C, both express the sodium/iodide symporter, a mammary carcinoma cell marker with potential therapeutic and diagnostic applications. All of the cell lines express estrogen receptor (ER) alpha and ER beta mRNA, and Western blot analysis demonstrates that the ER alpha protein is down-regulated in the M6 and M6C cell lines. M28N2 cells also express progesterone receptor (PgR), which is very unusual in a mouse mammary carcinoma cell line. In addition, all of the cell lines display growth inhibition when plated in media supplemented with charcoal-stripped fetal calf serum (CS FBS). When CS FBS is supplemented with beta estradiol or the progestin MPA, no significant difference in growth rates is observed relative to growth in CS FBS. The development and characterization of a progressive series of new mammary carcinoma cell lines will aid in the study of mammary carcinoma progression both in vitro and in vivo.
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PMID:Development and characterization of a progressive series of mammary adenocarcinoma cell lines derived from the C3(1)/SV40 Large T-antigen transgenic mouse model. 1260 5

Steroid hormones and their receptors are involved as initiators or promoters in prostate carcinogenesis. The intrauterine-perinatal period and maternal estrogen and testosterone levels have been proposed to be of etiologic importance in prostate tumorigenesis and cancer progression. The objective of this study was to analyze genetic polymorphisms in the androgen receptor ARStuI by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and in the estrogen receptor ER325 by PCR-single-strand conformational polymorphism (PCR-SSCP). In our study of 170 prostate cancer patients, ARStuI and ER325 genotypes and their association with disease progression and metastasis were analyzed. Age-adjusted logistic regression analysis indicates the association of ARStuI S1 allele with high-grade tumor (P = 0.033; OR = 3.0, 95% CI = 1.1-8.3) and the association of ER325 with high-grade tumor (P = 0.003; OR = 3.0, 95% CI = 1.4-6.4), advanced disease (P = 0.020; OR = 2.4, 95% CI = 1.1-5.1), risk of progression (P = 0.027; OR = 2.5, 95% CI = 1.1-5.7) and the presence of metastatic disease (P = 0.006; OR = 3.1, 95% CI = 1.4-6.8). In summary, this study has demonstrated androgen receptor (ARStuI) and estrogen receptor (ER325) genetic polymorphisms in prostate cancer patients and its association with disease progression and metastasis. Our results support the hypothesis that genetic factors related to steroid hormone receptors may influence the behavior of human prostate cancer.
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PMID:Steroid hormone genotypes ARStuI and ER325 are linked to the progression of human prostate cancer. 1260 25

Breast carcinomas represent a heterogeneous group of tumors, with a diverse biologic behavior, outcome, and response to therapy. Recent studies have demonstrated that alterations in the expression of adhesion molecules in cancer cells are related to aggressiveness and poor prognosis. The aim of our study was to investigate the expression of P-cadherin in breast carcinomas and correlate it with estrogen receptor (ER) status. We selected 73 ductal carcinomas in situ (DCIS) and 149 invasive carcinomas of the breast, and assessed the expression of P-cadherin as well as other biologic markers. P-cadherin expression showed a strong inverse correlation with ER expression in both types of breast carcinoma (in situ and invasive). P-cadherin-positive and ER-negative tumors were related to a higher histologic grade, a high proliferation rate, and expression of c-erbB-2. We demonstrated that P-cadherin identifies a subgroup of breast carcinomas that lacks ER expression, and correlates with higher proliferation rates and other predictors of aggressive behavior. We believe that these tumors represent an advanced step in cancer progression, and our data support the hypothesis that an estrogen-independent pathway regulates P-cadherin expression.
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PMID:Aberrant P-cadherin expression: is it associated with estrogen-independent growth in breast cancer? 1260 56

Drug resistance to tamoxifen (Tam) is a significant clinical problem but the mechanism through which this occurs remains elusive. We have developed a number of xenograft models of Tam-stimulated growth that model breast cancer progression using estrogen receptor positive MCF-7 or T47D breast cancer cells. When estrogen-stimulated T47D:E2 tumors are treated long term with Tam, Tam-stimulated tumors develop (T47D:Tam) that are stimulated by both estrogen and Tam. When HER-2/neu status is determined, it is clear that the T47D:Tam tumors express significantly higher levels of HER-2/neu protein by immunohistochemistry and mRNA as measured by real-time RT-PCR. The T47D:Tam tumors also express higher levels of estrogen receptor and progesterone receptor protein than their estrogen-stimulated T47D:E2 counterparts. We compared out results to the MCF-7 model of Tam-stimulated growth. The MCF-7:Tam ST (estrogen- and Tam-stimulated) and MCF-7:Tam LT (estrogen-inhibited, Tam-stimulated) were bilaterally transplanted to account for any mouse to mouse variation and characteristic growth patterns were observed. TUNEL staining was performed on MCF-7:Tam LT treated with either estrogen or Tam and it was concluded that estrogen-inhibited tumor growth was a result of increased apoptosis. Three phases of tumor progression are described that involve increases in HER-2/neu expression, de-regulation of estrogen receptor expression and increases in apoptosis which in concert determine the phenotype of drug resistance to Tam.
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PMID:A mechanism of drug resistance to tamoxifen in breast cancer. 1265 Jul 3

In cultured neuroblastoma cells, hypoxia induces a dedifferentiated phenotype. We tested whether hypoxia-induced dedifferentiation also occurs in vivo in mammary ductal carcinoma in situ with its well-defined lesions and distinct areas of necrosis. Ductal carcinoma in situ cells surrounding the central necrosis have high hypoxia inducible factor-1alpha protein levels, down-regulated estrogen receptor-alpha, and increased expression of the epithelial breast stem cell marker cytokeratin 19; lose their polarization; and acquire an increased nucleus/cytoplasm ratio, hallmarks of poor architectural and cellular differentiation. The hypoxia-induced changes were confirmed in cultured breast cancer cells. We propose that hypoxia-induced dedifferentiation is a mechanism that promotes tumor progression in breast cancer.
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PMID:Hypoxia promotes a dedifferentiated phenotype in ductal breast carcinoma in situ. 1267 Aug 86

Bone morphogenetic protein 7 (BMP-7) is an important regulator of cell development and differentiation of various organs. Tumorigenesis and tumor progression are also strongly associated with changes of the fate of cells which are highly differentiated in healthy tissues. Therefore, we studied the role of BMP-7 in breast cancer cell lines and in breast tumor tissue samples. BMP-7 is expressed in various cell lines, but in a cell line specific manner. The breast cancer cell lines MCF-7 and SK-BR-3 showed BMP-7 expression on the mRNA level. In T-47D we were not able to detect BMP-7 on the mRNA but on the protein level. Additionally, epidermal growth factor (EGF), a stimulator of proliferation, was not able to enhance BMP-7 expression on the transcriptional level. These findings are in contrast to the EGF-dependent regulation of BMP-6, indicating a differential regulation of these closely related TGF-beta members. In order to confirm the data obtained from cell cultures, we analyzed normal breast tissue and tumor tissue samples from 170 invasive ductal carcinomas of the breast by immunohistochemistry. We found BMP-7 expression in normal breast tissue in the end buds, but not in the ductus lactiferus. BMP-7 protein was detected in all 170 tumor samples. Comparing BMP-7 levels with histopathological parameters, we could not show a correlation of BMP-7 and the proliferation index nor with erbB receptors. But the expression of BMP-7 was highly correlated with estrogen receptor levels (p< or=0.01) and progesterone receptor levels (p< or =0.01) which are important markers for breast cancer prognosis and therapy.
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PMID:Differential expression and regulation of bone morphogenetic protein 7 in breast cancer. 1279 80

Members of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors are involved in the regulation of proliferation and differentiation of the mammary gland. In order to investigate the role of C/EBPalpha, -beta and -delta in breast cancer, we performed western blot analysis and partly immunohistochemistry in 75 mammary carcinomas, 10 normal mammary tissue samples and four mammary cell lines. Expression levels of both C/EBPalpha isoforms, C/EBPbeta isoforms LAP1, LAP2 (liver-enriched transcriptional activating proteins), and LIP (liver-enriched transcriptional inhibitory protein), and C/EBPdelta in the tumors were correlated with clinicopathological tumor parameters, expression of estrogen and progesterone receptors (ER, PR), Ki67 immunostaining, and expression of seven cell-cycle regulatory proteins which had been analyzed before. High C/EBPalpha and -delta protein levels correlated significantly with expression of cell-cycle promoters (cyclin D1 and E) and cell-cycle inhibitory proteins (Rb, p27, p16), but with none of the established prognostic parameters. In contrast, statistically significant relationships of the full-length C/EBPbeta isoform LAP1 and a negative estrogen receptor status, high grading, nodal involvement, and high cyclin E and p16 expression were found. For the shorter isoform LIP, correlations with an ER-negative phenotype and high Ki67 immunostaining were detected, and high histological grading (G3) correlated with lower LAP/LIP ratio. These results suggest that high C/EBPbeta expression might be involved in tumor progression and indicative of an unfavorable prognosis.
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PMID:Expression of the CCAAT/enhancer-binding proteins C/EBPalpha, C/EBPbeta and C/EBPdelta in breast cancer: correlations with clinicopathologic parameters and cell-cycle regulatory proteins. 1282 52

An increase in fibroblast growth factor-1 (FGF-1) is established as part of the cause of several important cancers including breast cancer, but the mechanisms by which it induces malignant behavior are not known. We now report that the protein 80K-H, a substrate for PKC, appears to be part of this mechanism and that it is increased in breast cancer and localizes to the nucleus as part of the mechanism. Our conclusion is based on an examination of a total of 58 biopsy specimens from human breast cancer patients for the presence of relationships between the 80K-H protein and the following: fibroblast growth factor receptor-1 (FGFR-1), tumor grade, microvessel counts (MVC), estrogen receptor (ER) and progesterone receptor (PgR) status. Based on histological grading and immunohistochemical (IHC) assays, we found strong direct relationships between 80K-H and FGFR-1 (r = 0.49, p = 0.003) and tumor grade (r = 0.42, p = 0.006). A trend for a direct relationship was observed with PgR (r=0.27, p=0.087). Notably, 80K-H immunostaining was largely limited to the epithelial cells of the mammary ducts. Subsequently, we studied the effects of FGF-1 on 80K-H in cultured human mammary carcinoma epithelial cells in order to establish a more direct relationship between these two molecules. We observed that FGF-1 treatment of MCF-7 cells stimulated translocation of 80K-H protein to the cell nucleus, as demonstrated by subcellular fractionation studies. Maximal intranuclear 80K-H was observed approximately 30 minutes following FGF-1 treatment. In addition, FGF-1 treatment of MCF-7 cells increased growth and invasion of MCF-7 cells, as demonstrated by cell proliferation and a modified Boyden chamber assay, respectively. Further support for 80K-H nuclearization was provided by the immunostaining of human breast cancer specimens and computer-assisted identification of a putative nuclear localization signal (NLS) near the amino terminus of 80K-H protein structure. These data support the existence of a previously unrecognized FGF-1/80K-H nuclear pathway in progression of human breast cancer and suggest that 80K-H may be useful for the assessment of breast tumor progression.
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PMID:Elevated 80K-H protein in breast cancer: a role for FGF-1 stimulation of 80K-H. 1284 77


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