Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E-cadherin is a Ca(2+)-dependent cell adhesion molecule which plays an important role in normal growth and development via mediation of homotypic, homophilic cell-cell interaction. Recent studies suggest that E-cadherin may be important in neoplastic progression as well, particularly as a suppressor of invasion. We have previously demonstrated that the invasive phenotype of rat prostate cancer cells is associated with the decreased expression of E-cadherin (M. J. G. Bussemakers, R. J. A. Van Moorselaar, L. A. Giroldi, T. Ichikawa, J. T. Isaacs, F. M. J. Debruyne, and J. A. Schalken, Cancer Res., 52:2916-2922, 1992). This is of particular interest, since the locus to which the human E-cadherin gene is mapped is frequently involved in allelic loss in prostate cancer (B. S. Carter, C. M. Ewing, W. S. Ward, B. F. Treiger, T. W. Aalders, J. A. Schalken, J. I. Epstein, and W. B. Isaacs, Proc. Natl. Acad. Sci. USA, 87:8751-8755, 1990; U. S. Bergerheim, K. Kunimi, V. P. Collins, and P. Ekman, Genes, Chromosomes Cancer, 3: 215-220, 1991). Impaired E-cadherin function is likely to be associated with aberrant expression of the protein. We therefore analyzed E-cadherin expression in situ by immunohistochemistry in nonmalignant and malignant specimens of human prostatic tissue. Of 92 tumor samples of either primary or metastatic deposits of prostate cancer, 46 had reduced or absent E-cadherin staining when compared to nomalignant prostate, which uniformly stained strongly positive. There was a statistically significant correlation between the decreased expression of E-cadherin and loss of tumor differentiation. Additionally, certain tumors within a histologically similar group could be distinguished by the presence of mixed populations of E-cadherin-negative and -positive cells. The percentage of tumors with aberrant E-cadherin staining increased when clinically localized tumors were compared to either tumors with extensive local progression or metastatic deposits of prostate cancer, suggesting a correlation between loss of E-cadherin and tumor progression. Taken together, these findings suggest that further exploration of E-cadherin as a candidate invasion suppressor molecule in human prostate cancer is warranted.
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PMID:Expression of the cellular adhesion molecule E-cadherin is reduced or absent in high-grade prostate cancer. 151 67

Decreased levels of the cell-cell adhesion molecule E-cadherin are associated with loss of differentiation in a number of human carcinomas. However, the value of E-cadherin as a prognostic marker in these cancers is largely undetermined. A previous study of E-cadherin levels in prostate cancer revealed that almost 50% of tumors examined had reduced or absent levels of this protein (Umbas et al., Cancer Res., 52: 5104-5109, 1992). To determine the potential prognostic significance of this finding, prostate cancer specimens from 89 patients were evaluated immunohistochemically for E-cadherin expression, and the results were related to histopathological grade, tumor stage, presence of metastases, and survival. As previously observed, a significant inverse correlation was found between E-cadherin expression and tumor grade. Importantly, we also found significant correlations between E-cadherin expression and tumor stage and overall survival. Sixty-three percent of the tumors that extended beyond the prostate capsule (T3-4) versus 33% of the tumors confined to the prostate (T1-2) had aberrant expression (chi 2 = 8.1, P < 0.005). Seventy-six percent of the primary tumors from patients that presented with metastases showed aberrant staining compared to 32% from patients without metastases (chi 2 = 14.9; P < 0.001). The life table analysis showed a significantly higher survival rate for patients with normal staining compared to patients with aberrant expression (chi 2 = 20.4, P < 0.001 by log rank test). Moreover, abnormal expression of E-cadherin correlated significantly with progression after radical prostatectomy (P < 0.005). These results suggest that E-cadherin expression can serve as a prognostic indicator for the biological potential of prostate cancer.
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PMID:Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. 751 46

CD44 is a glycosylated adhesion molecule which may undergo alternative splicing of 10 possible exons to generate variant isoforms. A number of CD44 variant isoforms expressed by tumor cells have been correlated with metastatic and proliferative behavior. In this study, we have characterized CD44 isoform expression on three prostate cancer cell lines: ALVA-31, PPC-1, and LNCaP. Using reverse transcriptase-polymerase chain reaction, we have found that ALVA-31 and PPC-1 cells express multiple CD44 isoforms, including CD44s (standard form), CD44E (epithelial form), and an exon 14-containing form. In addition, two smaller forms have been detected: one using an alternative donor splice site within exon 5, and a novel form omitting exon 5 entirely. The CD44 isoforms expressed by ALVA-31 and PPC-1 cells appear to be preferentially located on the cell surface. By contrast, LNCaP cells do not express any of the CD44 forms at the RNA or protein level. Both PPC-1 and ALVA-31 cells display tumorigenesis and invasiveness in nude mice, whereas LNCap cells exhibit a less malignant phenotype, suggesting a correlation between CD44 variant (CD44v) expression and aggressive prostate tumor behavior. Functional characterization reveals that CD44 mediates prostate cell adhesion to extracellular hyaluronic acid (HA). In addition, the CD44 cytoplasmic domain binds specifically to ankyrin, a membrane cytoskeletal protein. Double immunofluorescence labeling and confocal microscopic analyses indicate that HA binding induces the HA receptor (i.e., CD44) to form capped structures. Importantly, intracellular ankyrin is preferentially accumulated underneath HA receptor-capped structures. These results suggest that cytoskeletal proteins such as ankyrin are closely associated with CD44-mediated signaling events induced by HA. Finally, HA-mediated transmembrane interactions between CD44 isoforms and cytoskeletal proteins (i.e. ankyrin) may play a pivotal role in regulating tumor cell behavior during human prostate cancer development.
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PMID:Interaction of CD44 variant isoforms with hyaluronic acid and the cytoskeleton in human prostate cancer cells. 754 57

There is convincing evidence that a reduced expression of the E-cadherin cell-cell adhesion molecule associates with low tumor grade and poor prognosis in prostate cancer patients. However, little is known on how E-cadherin levels are regulated in human prostate cancer cells. We have inspected the effect of both androgens and estrogen on the expression of E-cadherin in the hormone-responsive LNCaP prostate tumor cell line, which is endowed with both androgen and estrogen receptors. Using both Dot Blot analysis and immunocytochemistry we have observed that either steroid significantly increased E-cadherin levels in these cells; this effect was not reversed by the simultaneous addition of the relevant antagonist, hydroxyflutamide or ICI-182,780.
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PMID:Sex steroids up-regulate E-cadherin expression in hormone-responsive LNCaP human prostate cancer cells. 762 77

Decreased E-cadherin expression assessed by immunohistochemistry correlates with poor survival of bladder and prostate cancer patients. The clinical usefulness of this parameter should therefore be evaluated in a large-scale prospective study. E-cadherin is an epithelial cell-cell adhesion molecule and impaired function presumably leads to increased invasive capacity of the cells. It has been shown that defective function can result from several mechanisms: mutation of the gene, alteration of transcription, posttranslational modification or changes in the interaction of E-cadherin with cytoskeleton anchoring proteins--the catenins. A major mechanism leading to decreased E-cadherin expression in tumors lies in decreased transcription of the gene. Hence, a better understanding of the regulation of E-cadherin transcription might open avenues for therapy by restoring normal expression.
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PMID:Defective E-cadherin function in urological cancers: clinical implications and molecular mechanisms. 765 35

Recently, we demonstrated that an androgen-regulated cell adhesion molecule, C-CAM, acts as a tumor suppressor in prostate cancer development. In this study, we further explored the possibility of applying C-CAM as a potential agent for developing prostate cancer gene therapy using an adenoviral delivery system. We found that prostate cancer cells, in general, were sensitive to adenoviral infection. In vitro characterization indicated that C-CAM1 protein was detected only in C-CAM1 adenovirus-infected cells but not in antisense control virus-infected cells, and the levels of expression showed dose dependency. Because of the stability of the protein, C-CAM expression in viral-infected cells appeared to be a long-lasting event, indicating that C-CAM may be superior to many other known tumor suppressors that have a short protein half-life. Most importantly, the delivery of a single dose of C-CAM adenovirus was able to repress the growth of PC-3-induced tumors in nude mice for at least 3 weeks. Taken together, these data indicate that C-CAM is a potential candidate for human prostate cancer therapy.
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PMID:Application of a tumor suppressor (C-CAM1)-expressing recombinant adenovirus in androgen-independent human prostate cancer therapy: a preclinical study. 779 10

We recently demonstrated that C-CAM, an epithelial-cell adhesion molecule of the immunoglobulin supergene family, could be regulated by androgen and might act as a growth repressor during differentiation of the prostatic epithelium. To define the role of C-CAM in prostatic tumorigenesis, a tumorigenic human prostatic cancer cell line, PC-3, was transfected with an expression plasmid containing C-CAM1 (a C-CAM isoform). Transfected clones showed significantly lower growth rates, reduced anchorage-independent growth, and less tumorigenicity in vivo than control cells. Furthermore, transfection of an antisense vector into a nontumorigenic prostatic epithelial cell line, NbE, resulted in tumor formation in nude mice. Sublines derived from these NbE-induced tumors had lower levels of C-CAM than did control cells. These data suggest that C-CAM1 can function as a tumor suppressor in prostate tumorigenesis.
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PMID:Tumor suppressive role of an androgen-regulated epithelial cell adhesion molecule (C-CAM) in prostate carcinoma cell revealed by sense and antisense approaches. 780 32

Decreased expression of the Ca(2+)-dependent cell adhesion molecule E-cadherin is observed in several poorly differentiated carcinomas and is presumably associated with an invasive phenotype of these tumors. Evidence accumulated so far indicates that decreased transcription is a major mechanism leading to defective E-cadherin function. Therefore, we isolated and characterized the human E-cadherin gene promoter and studied the transcriptional regulation of this gene in two human prostate cancer cell lines, one expressing E-cadherin (PC-3), the other one not expressing E-cadherin (TSU-pr1). We show that the E-cadherin promoter is not active in the non-expressing cells and that this may be due to the binding of a repressor protein to the promoter.
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PMID:Transcriptional regulation of the human E-cadherin gene in human prostate cancer cell lines: characterization of the human E-cadherin gene promoter. 809 45

The state of the art concerning major biological phenomenons of importance for current research on urological cancers is first briefly presented, followed by notes on the more outstanding presentations in this field. These notes are organized in a synthetic fashion, in order to point to the meaning of the hypotheses and findings presented, when taken together, as they pertain to the understanding of the mechanisms at play in urological cancers, as we see them in 1995. Some concepts seem to have now reached a point where we can expect to see some applications in a not so distant future: in prostate cancer, it is confirmed that the machinery of apoptosis is functional even in the hormone-insensitive cells, suggesting that its enhancement might be useful in these often difficult situations; techniques to detect circulating malignant cells, which have been greatly refined (RT-PCR of PSA and PSM), are now extremely sensitive and may prove unvaluable in providing intermediate end points to compare the relative efficacy of treatment regimens in clinical trials; the symposium on prostate cancer screening by PSA dosage was an excellent opportunity to review extensively the data available on this topic, but -as expected- it could not decide on some essential issues; in bladder tumors, data on the expression of adhesion molecules (CD44 variant) are still preliminary, but some provocative observations have been reported (presence on mature ARN, only in bladder cancer cells, of intronic sequences that have not been excised); in renal cell cancer, a considerable amount of knowledge has accumulated on the von Hippel-Lindau gene, a putative anti-oncogene, and work is in progress to define the function of its protein; finally, pathways essential to understanding and treating cancer have been dissected, particularly the apoptosis-proliferation network, and the involvement in it of p53, Waf-1 and the bcl-2 gene family cascade.
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PMID:[The annual meeting of the American Association for Cancer Research (AACR), Toronto (Ontario), 18-22 May 1995]. 867 62

CD44s (standard form of CD44) is a transmembrane glycoprotein whose external domain displays extracellular matrix adhesion properties by binding both hyaluronic acid (HA) and collagen. The cytoplasmic domain of CD44s interacts with the cytoskeleton by binding directly to ankyrin. It has been shown that post-translational modifications, such as phosphorylation (by protein kinase C), acylation (by acyl-transferase) and GTP-binding enhanced CD44's interaction with cytoskeletal proteins. Most importantly, the interaction between CD44s and the cytoskeletal protein, ankyrin, is required for the modulation of CD44s cell surface expression and its adhesion function. Recently, a number of tumor cells and tissues have been shown to express CD44 variant (CD44v) isoforms. Using RT-PCR and DNA sequence analyses, we have found that unique CD44 splice variant isoforms are expressed in both prostate and breast cancer cell lines and carcinomas. Most importantly intracellular ankyrin is preferentially accumulated underneath the patched/capped structures of CD44 variant isoform in both breast and prostate cancer cells attached to HA-coated plates. We propose that selective expression of CD44v isoforms unique for certain metastatic carcinomas and their interaction with the cytoskeleton may play a pivotal role in regulating tumor cell behavior during tumor development and metastasis.
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PMID:Involvement of CD44 and its variant isoforms in membrane-cytoskeleton interaction, cell adhesion and tumor metastasis. 875 Jan 86


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