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

Despite its high incidence and mortality rate, the molecular mechanisms underlying the oncogenesis and progression of prostate cancer are still unclear. This review, based on recently published data, surveys the current state of knowledge of human prostate oncogenesis, dealing with genetic predisposition in familial clusters of prostate cancer, providing new information on the somatic genetic alterations, which have been approached in four ways (measurement of DNA content, cytogenetic analysis, in situ hybridization, and molecular analysis), and investigating the problems of androgen independence and intratumour heterogeneity in prostate tumours. Lastly, the potential clinical applications of the genetic alterations, which may become important in the near future, are addressed.
 ...
PMID:Genetic aspects of prostate cancer. 964 38

The PTEN/MMAC1/TEP1 gene, located at 10q23.3, is a tumor suppressor gene responsible for the familial cancer syndromes Cowden disease and Bannayan-Zonana syndrome, and is commonly somatically mutated in several types of cancers. Mutations of the PTEN gene have been found in prostate cancer cell lines and LOH at 10q22-24 in prostate tumors have also been described with a high frequency. To determine the role of this gene in prostate tumorigenesis, we therefore analysed 22 primary tumors for loss of heterozygosity (LOH) within the 10q22-23 region such that tumors hemizygous at those loci may be examined for somatic PTEN mutations. Losses of heterozygosity of at least one locus was found in 12 (55%) of the 22 tumors DNAs. Among these, six tumors exhibited allele loss in the interval between D10S1765 and D10S541 wherein lies the PTEN gene. We searched the entire coding region of PTEN for somatic mutations in these six tumors. One somatic mutation (17%), a 1 bp deletion, was detected in exon 7 of the gene, in one tumor, indicating that somatic mutations of the PTEN gene may occur in primary prostate tumors.
 ...
PMID:PTEN/MMAC1/TEP1 involvement in primary prostate cancers. 967 8

Autocrine growth factors for the epidermal growth factor receptor (EGFR) have been identified in prostate tumors, implicating a role for EGFR in the progression of prostate cancer. To investigate early signaling mechanisms used by the EGFR in prostate tumor cells, we have characterized the involvement of the Shc (src homology 2/x-collagen related) adapter protein in EGFR signaling in several human prostate tumor cell lines. In androgen-responsive lymph node-prostate cancer (LNCaP) cells and androgen-insensitive PC3, DU145 and PPC-I cells, Shc was identified as one of the most prominent phosphotyrosine proteins to be elevated in response to EGF. Equivalent levels of the 46- and 52-kDa Shc isoforms were detected in all of the tumor cell lines tested. However, levels of the 66-kDa isoform were variable among the cell lines. In all of the tumor cell lines, EGF caused an association between Shc and Grb2, another adapter protein linked to cellular ras activation. Additionally, several phosphotyrosine proteins, including a 115-120-kDa protein in EGF-treated LNCaP cells, co-associated with Shc. The profile of these Shc-associating proteins, however, differed among the tumor cell lines. Our results indicate that Shc is a common downstream element of EGFR signaling in prostate tumor cells and suggest multiple functions for Shc in prostate tumorigenesis.
 ...
PMID:Involvement of Shc in the signaling response of human prostate tumor cell lines to epidermal growth factor. 971 65

A high-fat diet increases the risk of colon, breast and prostate cancer. The molecular mechanism by which dietary lipids promote tumorigenesis is unknown. Their effects may be mediated at least in part by the peroxisome proliferator-activated receptors (PPARs). These ligand-activated nuclear receptors modulate gene expression in response to fatty acids, lipid-derived metabolites and antidiabetic drugs. To explore the role of the PPARs in diet-induced carcinogenesis, we treated mice predisposed to intestinal neoplasia with a synthetic PPARgamma ligand. Reflecting the pattern of expression of PPARgamma in the gastrointestinal tract, treated mice developed a considerably greater number of polyps in the colon but not in the small intestine, indicating that PPARgamma activation may provide a molecular link between a high-fat diet and increased risk of colorectal cancer.
 ...
PMID:Activators of the nuclear receptor PPARgamma enhance colon polyp formation. 973

Genomic aberrations at the chromosome 16q arm are one of the most consistent abnormalities observed by loss of heterozygosity and comparative genomic hybridization analyses in human prostate cancer, suggesting that there are tumor suppressor or metastasis suppressor genes encoded by this chromosomal region. To functionally identify such suppressor genes, we have conducted microcell-mediated chromosome transfer to introduce human chromosome 16 into the highly metastatic Dunning rat prostatic cancer cell line, AT6.1. The metastatic ability of the resultant microcell hybrid clones was then tested in a standard spontaneous metastasis assay using SCID mice. When the microcell-mediated chromosome transfer hybrid cells containing whole human chromosome 16 were injected, the number of metastatic lesions in the lung was significantly reduced as much as 99% on average. Therefore, chromosome 16 has a strong activity to suppress the metastatic ability of AT6.1 cells while it did not affect the tumorigenesis and tumor growth rate. A PCR analysis of various microcell hybrid clones with sequence-tagged site markers indicates that the metastasis suppressor activity is located in the q24.2 region of chromosome 16. Our results are consistent with the previous finding that the region of human chromosome 16q has frequent loss of heterozygosity in prostate cancer patients and suggest that there is a metastasis suppressor gene in this region that may play an important role in the progression of prostate cancer.
 ...
PMID:Human chromosome 16 suppresses metastasis but not tumorigenesis in rat prostatic tumor cells. 978 3

To clarify the role in prostate tumorigenesis played by loss of the three known or putative tumor suppressor loci on the centromeric portion of chromosome 13q, we examined 80 clinically localized and 15 advanced prostate carcinomas for allelic loss at microsatellite markers mapped to this region, including markers tightly linked to the BRCA-2, retinoblastoma (Rb), and DBM (deleted in B-cell malignancy) loci. Among the 80 clinically localized cases, 24 showed allelic loss at one or more 13q loci. In all cases with loss, the Rb and/or DBM loci were lost. No cases were found with loss of Rb without loss of DBM or loss of DBM without loss of Rb, implying a role for both the Rb and DBM loci in clinically localized prostate cancer. Loss of the BRCA-2 locus was less common (4 of 55 informative cases) and was always associated with loss of Rb and/or DBM loci. Thus, the BRCA-2 locus does not appear to play as important a role in clinically localized prostate cancer as the Rb and/or DBM loci. Allelic loss on 13q was extremely common in the clinically advanced cases; it was present in 14 of the 15 cases. The rate of allelic loss at each of the three tumor suppressor loci was increased significantly in the advanced cases (P < 0.01, Fisher's exact test). Thus, loss of heterozygosity on 13q is very common in prostate cancer and occurs at all three known or putative tumor suppressor loci on the centromeric portion of chromosome 13q.
 ...
PMID:Allelic loss on chromosome 13q in human prostate carcinoma. 981 75

Insulin-like growth factor-binding protein-related protein-1 (IGFBP-rP1; also known as Mac25, TAF, and PSF) is a member of the IGFBP superfamily. It is a cysteine-rich protein that shares structural and functional similarities with the conventional IGFBPs. In situ hybridization of prostate tissue sections show intense IGFBP-rP1 messenger ribonucleic acid (mRNA) expression in normal stroma and glandular epithelium. There was a significant loss of detectable IGFBP-rP1 mRNA in metastatic prostate tissue. IGFBP-rP1 mRNA (Northern blots) and protein (immunoblots) were detectable in primary cultures ofprostatic stromal and epithelial cells as well as in the immortalized nonmalignant prostatic human epithelial cells, P69, and in the P69 metastatic subline, M12. IGFBP-rP1 expression was not detectable in the prostatic cancer cell lines PC-3, DU145, and LNCaP. IGFBP-rP1 expression was regulated in P69 cells but not in M12 cells. Protein and mRNA expression was up-regulated by IGF-I, transforming growth factor-beta, and retinoic acid. The observations that IGFBP-rP1 expression is significantly diminished in prostate tumorigenesis and is regulated in nonmalignant prostate cells suggest IGFBP-rP1 is important in normal prostatic cell growth.
 ...
PMID:Characterization of insulin-like growth factor-binding protein-related protein-1 in prostate cells. 985 77

A transgenic mouse model of metastatic prostate cancer has been developed that is 100% penetrant in multiple pedigrees. Nucleotides -6500 to +34 of the mouse cryptdin-2 gene were used to direct expression of simian virus 40 T antigen to a subset of neuroendocrine cells in all lobes of the FVB/N mouse prostate. Transgene expression is initiated between 7 and 8 weeks of age and leads to development of prostatic intraepithelial neoplasia within a week. Prostatic intraepithelial neoplasia progresses rapidly to local invasion. Metastases to lymph nodes, liver, lung, and bone are common by 6 months. Tumorigenesis is not dependent on androgens. This model indicates that the neuroendocrine cell lineage of the prostate is exquisitely sensitive to transformation and provides insights about the significance of neuroendocrine differentiation in human prostate cancer.
 ...
PMID:A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells. 986 Sep 77

Prostate cancer is the most common cancer amongst males in developed countries. Surgical removal of the prostate effectively cures the primary disease but the metastatic disease is refractory to most forms of chemotherapy. There is a clinical need to develop novel treatment strategies that exploit the mode of action of both conventional and alternative drugs/medicinal plants. We have been investigating the anti-proliferative and anti-tumor effects of an herbal preparation termed PC-SPES (patent pending, US serial number 08/697, 920) which is a refined powder of eight different medicinal plants. PC-SPES administered as a food supplement caused a dramatic decrease in prostate specific antigen levels in some prostate cancer patients with advanced disease. These preliminary clinical findings laid the foundation for a program to examine the in vitro and in vivo effects of PC-SPES, and identify the active component in this mixture so that a standardized treatment regimen can be formulated. In this communication, we report the anti-tumor effects of PC-SPES incorporated in the diet utilizing a well studied Dunning R3327 rat prostate cancer model. Dietary PC-SPES at levels of 0.05% and 0.025% did not exhibit any toxicity and no significant difference in food intake was noted at the end of six weeks. Dose dependent inhibitory effect of dietary PC-SPES was observed on both tumor incidence (P=0. 01) and rate of tumor growth when tumors were induced in syngeneic Copenhagen rats by intradermal injections of MAT-LyLu cells that are known to metastasize in the lung and lymph nodes. The number of pulmonary metastases in animals on PC-SPES that showed no primary tumor growth had no metastatic lesions in the lung, however, in animals that did not respond to PC-SPES, the number of pulmonary metastases was not significantly different from the non-treated controls. The significant anti-tumor effects of PC-SPES on MAT-LyLu induced tumorigenesis and metastasis in Copenhagen rats, in general refractory to most conventional therapy, suggests a therapeutic benefit of this herbal food supplement and may be a useful adjuvant to conventional therapeutic modalities.
 ...
PMID:Anti-tumor effects of PC-SPES, an herbal formulation in prostate cancer. 1008 19

Publications (up to the year 1997) on the interactions of "prostatic" kallikreins (prostatic specific antigen-PSA, etc.), sex hormones, insulin-like growth factors (IGF) and proteins binding them (IGFBP) in physiological processes (ageing, menstrual cycle, pregnancy) and oncogenesis (prostatic and mammary cancer) are reviewed. The concentrations of PSA, IGF, and IGFBP in organs and liquid media of men and women are presented. A concept of similarity in the mechanisms of interactions of sex hormones (dihydrotestosterone in men and progesterone in women), PSA, IGFBP, and IGF during activation of anabolic and proliferative processes in health and carcinogenesis is presented as a scheme. The diagnostic and prognostic value of PSA as a cancer marker should not be confined to male tumors (prostatic cancer and benign prostatic hyperplasia). Our data permits us to regard PSA as an oncofetal marker for men and women, indicating normal and neoplastic proliferative processes in the prostatic, mammary, salivary, and other glands and in the lungs and endometrium. Diagnostic and prognostic significance of PSA in breast cancer is shown. The traditional name "PSA" does not reflect its physiological and pathogenetic role as a member of the kallikrein family with chymotrypsin-like activity. PSA is not absolutely specific towards the producer organ and sex. Its relative specificity for the prostate is undoubted, because the content of PSA in prostatic tissue and seminal plasma is 10(6)-10(8) times higher than in the serum and other organs of men and women. Therefore, although the terms "prostatic, "specific", and "antigen" now became trivial and it is difficult to refuse from them, they can be used only in quotation marks.
 ...
PMID:["Prostatic" kallikreins, sex hormones and insulin-like growth factors: complex of male and female regulatory elements in health and carcinogenesis]. 1022 33


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>