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)

Overexpression of c-myc protein and amplification of c-myc were investigated by immunohistochemistry and differential polymerase chain reaction (dPCR) in 440 formalin-fixed primary breast carcinoma tissues, respectively. Overexpression of c-myc was detected in 45% (199/440) and amplification of c-myc was observed in 25% (112/440) of the primary breast carcinomas. Immunolocalization of c-myc oncoprotein was demonstrated in 35% (8/23) of the comedo subtype, 17% (3/18) of the non-comedo subtype, 37% (15/41) of the comedo DCIS and 49% (20/41) of the adjacent invasive ductal carcinomas, 21% (4/19) of the non-comedo DCIS and 37% (7/19) of the adjacent invasive lesions, 49% (133/270) of the invasive ductal carcinomas, 33% (11/33) of the invasive lobular carcinomas, 29% (6/21) of the colloid carcinomas and 47% (7/15) of the medullary carcinomas. C-myc was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 24% (10/41) of the adjacent invasive ductal carcinomas, 30% (82/270) of the invasive ductal carcinomas, 21% (7/33) of the invasive lobular carcinomas, 14% (3/21) of the colloid carcinomas and 24% (4/15) of the medullary carcinomas. Amplification of c-myc was noted in 16% (3/9) of the invasive ductal carcinomas but not in the adjacent non-comedo DCIS lesions. A significant association (P<0.05) was observed between in situ components and adjacent invasive lesions for c-myc expression and amplification. Overexpression of c-myc protein was significantly correlated with poorly differentiated (P<0.05) and high proliferation index (Ki-67) (P<0.05) tumors but not with lymph node metastases (P>0.05), patient age (P>0.05) and estrogen receptor status (P>0.05). Significant relationship was also noted between amplification of c-myc and absence of estrogen receptor (P<0.05), high histological grade (P<0.05) and high proliferation index (Ki-67) (P<0.05). No relationship was seen with nodal status (P>0.05) and patient age (P>0.05). Majority of the Malaysian female patients are from younger age group (<50 years old) but overexpression and amplification of c-myc was not statistically associated with patient age (P>0.05) indicating that these alterations may be independent events of patient age. The above observations suggest that overexpression and amplification of c-myc could play an important role in tumor progression from non-invasive to invasive and, also, it may have the potential as a marker of poor prognosis of breast cancer.
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PMID:Protein expression and molecular analysis of c-myc gene in primary breast carcinomas using immunohistochemistry and differential polymerase chain reaction. 1178 32

Fibulin-1 is an extracellular matrix protein induced by estradiol in estrogen receptor (ER) positive ovarian cancer cell lines. Alternative splicing of fibulin-1 mRNA results in four different variants named A, B, C and D that may have distinct biological functions. We studied the relative expression of fibulin-1 mRNA variants and their estrogen regulation in human ovarian cancer cells. In ovarian tissues and cancer cell lines, fibulin-1C and -1D are the predominant forms, whereas fibulin-1A and -1B are weakly expressed. We developed a competitive PCR assay based on coamplification of fibulin-1C and -1D to study the relative expression of these fibulin-1 variants in human ovarian samples. In ovarian cancer cell lines and ovarian cancer samples, there was a marked increase in the fibulin-1C:1D and fibulin-1C:HPRT mRNA ratios as compared to normal ovaries. In the BG1 estrogen receptor positive ovarian cancer cell line, fibulin-1C mRNA was induced by estradiol in a dose- and time-dependent manner. Since others and we have previously shown an increased expression of ERalpha as compared to ERbeta in ovarian cancer cells, we investigated whether ERalpha or ERbeta is involved in this induction. For this aim, MDA-MB-231 breast cancer cell line, which expresses both low basal levels of ERs and fibulin-1, was infected with recombinant ERalpha or ERbeta encoding adenovirus and treated with estradiol. Fibulin-1C was induced by estradiol in ERalpha- but not ERbeta-infected cells, suggesting that fibulin-1C induction is mediated through ERalpha. In ovarian tumors, a trend towards a correlation between fibulin-1C and ERalpha expression levels was noted. In conclusion, this study showed an increased fibulin-1C:-1D mRNA ratio in ovarian cancer cells as compared to normal ovaries. This finding suggests that the C variant may be involved in ovarian carcinogenesis. Fibulin-1C overexpression may thus be a clue for the understanding of a putative role of estrogens in ERalpha promoted ovarian tumor progression.
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PMID:Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells. 1185 Aug 27

To evaluate the significance of murine double minute 2 (MDM2) oncoprotein in human breast cancer as a nuclear-cytoplasmic shuttling protein, an estrogen receptor (ER) alpha regulator, and a prognostic marker and to study how MDM2 is overexpressed, we investigated its status in tissue samples and examined the correlation between overexpression and MDM2 gene abnormalities, status, and clinicopathological parameters. We detected MDM2 oncoprotein in both nucleus and cytoplasm by frozen-section immunohistochemistry. There was a significant correlation between MDM2 overexpression and low-grade nuclear atypia, absence of lymph node involvement, and increased levels of ER alpha protein. Our molecular assays found no point mutations in Ser17, but there was a correlation between MDM2 overexpression and the lack of splice variant mRNAs. These results suggest that the distribution of MDM2 reflects its nuclear-cytoplasmic shuttling ability; that interaction between p53 and MDM2 for tumor progression is not enhanced by point mutations at codon 17; and that the expression of MDM2 splice variants is a reason for the lack of its overexpression. MDM2 overexpression correlates with favorable prognostic parameters. A decreased level of MDM2 will lead to a deviation from the ER alpha signaling pathway.
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PMID:Overexpression of MDM2 oncoprotein correlates with possession of estrogen receptor alpha and lack of MDM2 mRNA splice variants in human breast cancer. 1185 76

It has long been appreciated that the estrogen receptor (ER) plays an important role in the biology of breast cancer. It is an accepted factor predicting favorable disease outcome and treatment response, and as such is generally considered to represent a "good" prognostic marker in breast cancer. In this review we present data suggesting that the ER may also play a pivotal role in the metastatic behavior of breast cancer, and present an argument that the up-regulation of ER and/or the selection of specific ER mutations are early events important for facilitating tumor progression. Thus, ER could serve dual roles in breast cancer, acting as a "bad" prognostic marker later in the disease process.
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PMID:The role of estrogen receptors in breast cancer metastasis. 1201 30

It is well known that the functions of reproductive organs are regulated by sex steroids and their receptors and it is hypothesized that the progression of neoplasms that originate from the reproductive organs is influenced by them. However, the correlation between sex steroids and tumor progression, especially tumor invasion, is not well known in endometrial carcinoma. In our study, we focused on the influence of estrogen and its receptor in invasion and matrix metalloproteinases (MMPs), which are known to be important in tumor invasion, as well as on endometrial carcinoma cells. The growth of Ishikawa cells, to which an estrogen receptor-alpha expressing vector was transfected, was accelerated by 17 beta-estradiol as was the acceleration of the expression of cyclin D1. By invasion assay, in conditions with 17 beta-estradiol, the invasiveness of Ishikawa cells was enhanced. Furthermore, according to the accelerated invasiveness, the expression of MMP-1, -7 and -9 and Ets-1 was enhanced. These results suggest that activation of ER-alpha by estrogen results in tumor progression by stimulating cell growth and invasiveness via acceleration of the expression of MMPs.
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PMID:Acceleration of invasive activity via matrix metalloproteinases by transfection of the estrogen receptor-alpha gene in endometrial carcinoma cells. 1211 20

The tumor suppressor gene maspin has been reported to inhibit the invasiveness and motility of breast cancer cells. It has been reported that maspin is expressed in normal human mammary epithelial cells but is downregulated during cancer progression, and that p53 could induce maspin expression by transcriptional activation. However, to date, the clinical significance of maspin expression and its correlation with p53 protein expression in human breast cancer patients have not been elucidated. One hundred and sixty-eight female patients diagnosed with invasive ductal carcinoma, who had undergone a mastectomy (154 patients) or breast-conserving surgery (14 patients), were followed up for 15-119 months (median: 87 months) postoperatively. Immunoreactivity for maspin and p53 antibodies with paraffin-embedded carcinoma tissue was investigated using labeled streptavidin-biotin methods. Tumors with more than 20% of positive cells were considered positive for the expression of maspin. The expression of maspin in carcinoma cells was found in 27.4% (46 of 168) and significantly correlated with larger tumor size (p = 0.008), higher histologic grade (p = 0.0001) and positive p53 status (p = 0.003). A significant inverse relationship was observed between the expression of maspin and estrogen receptor (p = 0.0004) or progesterone receptor status (p = 0.02). Univariate analysis by log-rank test revealed a significant association between the expression of maspin and shorter relapse-free survival (p < 0.0001) and overall survival (p < 0.0001). According to Cox's multivariate analysis, the expression of maspin had the most significant effect in relapse-free survival (p < 0.0001) and overall survival (p < 0.0001) followed by lymph node status. In turn, the expression of maspin in 58 cases of ductal carcinoma in situ were also investigated to explore whether the downregulation of maspin through cancer progression are true or not. However, there were no positive cases in our series. These results seem to be contrary to previous reports defining maspin as a tumor suppressor gene. Although more precise characterization of the maspin expression, especially gene analysis is essential, the present investigation suggests that the expression of maspin is not downregulated through malignant progression and that the immunohistochemic detection of maspin in carcinoma cells may be helpful for selecting the group of breast cancer patients with an aggressive phenotype.
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PMID:Expression of maspin predicts poor prognosis in breast-cancer patients. 1211 29

Recent progress in the study of chromogranins has revealed that there are many novel peptides derived from chromogranin with their multiple pathophysiologic roles. To learn the possible roles of chromogranin in breast carcinoma, we immunohistochemically investigated tissue localization of chromogranin A (CgA) and chromogranin B (CgB) in 10 normal breast tissues, 23 noninvasive ductal carcinomas (NIDCs), and 169 invasive ductal carcinomas (IDCs) and compared their expression with estrogen receptor (ER), progesterone receptor (PR), and Ki67. CgA and CgB were sporadically detected in normal cells of the ducts, acini, and luminal secretion. The expression of CgA and CgB was higher in NIDCs than in IDCs: CgA = 70% of NIDC vs 22% of IDC and CgB = 65% of NIDC vs 30% of IDC. There was a statistical correlation between the expression of CgA and PR (p < 0.05) and CgB and ER (p < 0.05) in IDCs without lymph node metastasis. On the other hand, there was a significant correlation between expression of CgB and PR and an inverse correlation between CgA and Ki67 in IDCs of overall cases. The data suggest that CgA and CgB may play some role in the early phase of neoplastic progression.
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PMID:Chromogranin A and chromogranin B in noninvasive and invasive breast carcinoma. 1216 59

Transcription factor oncogenes such as GLI and c-MYC are central to the pathogenesis of human tumors. GLI encodes a zinc finger protein that is activated by Sonic Hedgehog signaling. Mutations in this pathway induce GLI expression in basal cell carcinoma, and expression of GLI in mice is sufficient to induce these skin tumors. We used microarrays to identify transcripts regulated by GLI or c-MYC after retroviral transduction and short-term culture of epithelial RK3E cells. Although each of these oncogenes induces malignant transformation of RK3E, two distinct sets of genes were identified. Of approximately 17,500 transcripts represented on the microarrays, GLI up-regulated the expression of 158 and repressed the expression of 52. In contrast, transcripts regulated by c-MYC were mainly repressed (424 of 682 regulated transcripts). Transcripts induced by the GLI transgene are likewise expressed in association with endogenous GLI in Ptch-deficient murine fibroblasts or in human skin tumors, but are not up-regulated in RK3E cells transformed by c-MYC, KLF4, or HRAS1. Unlike these other oncogenes, GLI induced the expression of mesenchymal cell markers including Snail, a zinc finger protein implicated in epithelial-mesenchymal transition in development and during tumor progression. A novel GLI-estrogen receptor fusion protein rapidly induced Snail mRNA expression in a manner like Ptch, a known direct transcriptional target gene. Induction of Snail expression and epithelial-mesenchymal transition by GLI may account for certain histopathological features of basal cell carcinoma, such as the absence of a well-defined, intraepithelial precursor lesion. In addition, consistent expression of the newly identified GLI-induced transcripts within GLI-expressing tumors in vivo indicates that oncogene-specific transcriptional profiles may be useful diagnostic tools for analysis of human tumors.
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PMID:Comparative gene expression profile analysis of GLI and c-MYC in an epithelial model of malignant transformation. 1238 50

Flavonoids, such as daidzein and genistein, present in dietary plants like soybean, have unique chemical properties with biological activity relevant to cancer. Many flavonoids and polyphenols, including resveratrol in red wine and epigallocatechin gallate in green tea, are known antioxidants. Some of these compounds have estrogenic (and antiestrogenic) activity and are commonly referred to as phytoestrogens. A yeast-based estrogen receptor (ER) reporter assay has been used to measure the ability of flavonoids to bind to ER and activate estrogen responsive genes. Recently, estrogenic compounds were also shown to trigger rapid, nongenomic effects. The molecular mechanisms, however, have not been completely detailed and little information exists regarding their relevance to cancer progression. As a preliminary step toward elucidating rapid phytoestrogen action on breast cancer cells, we investigated the effect of 17-beta estradiol (E2), genistein, daidzein and resveratrol on the activation status of signaling proteins that regulate cell survival and invasion, the cell properties underlying breast cancer progression. The effect of these estrogenic compounds on the activation, via phosphorylation, of Akt/protein kinase B (Akt) and focal adhesion kinase (FAK) were analyzed in ER-positive and -negative human breast cancer cell lines. E2, genistein and daidzein increased whereas resveratrol decreased both Akt and FAK phosphorylation in nonmetastatic ER-positive T47D cells. In metastatic ER-negative MDA-MB-231 cells, all estrogenic compounds tested increased Akt and FAK phosphorylation. The inhibitory action of resveratrol on cell survival and proliferation is ER dependent. Therefore, all estrogenic compounds tested, including resveratrol, may exert supplementary ER-independent nongenomic effects on cell survival and migration in breast cancer cells.
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PMID:Flavonoid effects relevant to cancer. 1242 74

Expression of death-associated protein (DAP) kinase, a proapoptotic serine/threonine protein kinase, is frequently lost in human tumors. In a study of 134 primary breast cancer specimens hypermethylation of the DAP kinase gene was found in 13% of cases. A highly significant difference (P < 0.001) of DAP kinase inactivation was observed between invasive lobular cancer (n = 19) and invasive ductal cancer (n = 85; 53% versus 9%, respectively). Hypermethylation correlated with loss of RNA expression, estrogen receptor positivity (P < 0.01), and the absence of p53 overexpression (P < 0.01). In contrast to invasive lobular cancer, the in situ-growing precursor lesion lacked epigenetic modification of the DAP kinase promotor by aberrant methylation indicating a potential role in tumor progression. Unlike the DAP kinase gene, hypermethylation of the cyclin D2 and RASSF1A genes did not correlate with a particular histological subtype or to invasiveness [corrected]. We conclude that different histological subtypes of breast cancer may not only differ concerning specific chromosomal abnormalities and DNA mutations but also with regard to epigenetic inactivation patterns.
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PMID:Promoter hypermethylation of the death-associated protein kinase gene in breast cancer is associated with the invasive lobular subtype. 1243 60


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