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)

To evaluate if there is any consistent relationship between the expression of intermediate filament proteins (IFP), particularly keratins, and the degree of malignancy of prostatic cancer cells, a series of nine Dunning rat prostatic cancer sublines that span the entire spectrum of progression of prostatic cancer were studied immunocytochemically by the use of a variety of antibodies specific for keratins, vimentin, or desmin. For the keratin studies, monoclonal antibodies with either a general reactivity to several keratins or highly specific for either luminal or basal epithelial cells of the normal rat prostate were used. By use of an antibody specific for luminal cell keratin 18, the luminal tumor cells of the well-differentiated, slow-growing H and HI-S sublines were positively stained. In most of the sublines with a more advanced state of progression (i.e., the moderately differentiated, moderately fast growing HI-M; the poorly differentiated, faster growing HI-F; and the anaplastic, very fast growing AT-1, AT-2, and MAT-Lu tumors), however, no expression of keratin specific for luminal cells was detected. In addition, several of the most advanced sublines (i.e., AT-1, AT-2, and MAT-Lu) were negative using any of the keratin antibodies. In contrast, several of the other sublines with the most advanced degree of progression (i.e., the anaplastic, very fast growing MAT-LyLu tumor derived from the AT-1 subline; and the anaplastic, very fast growing AT-3 tumor, derived from the HI-F subline), however, were positively stained with the keratin antibody specific for the luminal cells. By use of the keratin antibody specific for the basal cells of the normal rat prostate, the basal tumor cells of the well-differentiated slow-growing H and HI-S tumor were positively stained. This positive staining for basal cell keratin was also found in the HI-M and HI-F tumors, while the AT-1, AT-2, MAT-Lu, MAT-LyLu, and AT-3 were negative with this antibody. Thus, a loss in staining for basal cell keratin was consistently associated with the most advanced state of tumor progression. Vimentin-positive staining was demonstrated either alone or with keratin-positive staining in part of the epithelial cancer cells of all the sublines. An increase in the positive staining for vimentin was consistently associated with a more advanced state of tumor progression. Desmin-positive staining was found only in smooth cells present within the various tumor sublines.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intermediate filament expression and the progression of prostatic cancer as studied in the Dunning R-3327 rat prostatic carcinoma system. 266 36

Several immortalized and malignant adult human prostatic epithelial cell lines have recently been developed. The three most widely used carcinoma cell lines, DU-145, PC-3, and LNCaP, developed between 1977 and 1980, have greatly contributed to our present understanding of prostate cancer. Before a cell line can be accepted as having prostatic epithelial origin, some basic characteristics must be established. Expression of specific cytokeratins, but absence of desmin and factor VIII, should be first determined to establish epithelial origin. Responsiveness to androgens and expression of androgen receptor and prostate specific antigen should be examined under stringent culture conditions to establish prostatic epithelial origin. Response to growth factors and expression of their receptors facilitates further characterization of cell behavior. Cell lines immortalized by human papillomaviruses (HPVs) are of special interest because HPVs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV-18 immortalized cells with the ras oncogene provides cell systems for investigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinoma or resulted from immortalization with simian virus 40 (SV40) or HPV or was transformed in vitro by oncogenes. Comparisons of these characteristics should facilitate elucidation of the mechanisms involved in initiation, promotion, and progression of prostate cancer. These cell lines will further serve as useful models for investigating tumor progression, invasion, metastasis, new therapeutic strategies, drug resistance, and its reversal and chemoprevention. This review will be published in three parts and will summarize cell markers necessary for characterization, as well as the characteristics and some applications of the immortalized as well as malignant adult human prostatic epithelial cell lines. Part 1 deals with cell markers and the immortalized, nontumorigenic cell lines.
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PMID:Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications. Part I. Cell markers and immortalized nontumorigenic cell lines. 897 36

This is Part 2 of a three-part review and deals with tumorigenic cell lines. Several immortalized and malignant adult human prostatic epithelial cell lines have been recently developed. The three most widely used carcinoma cell lines-DU-145, PC-3, and LNCaP-developed between 1977 and 1980, have greatly contributed to our current understanding of prostate cancer. Before a cell line can be accepted as having prostatic epithelial origin, some basic characteristics must be established. Expression of specific cytokeratins but absence of desmin and factor VIII should be first determined to establish epithelial origin. Responsiveness to androgens and expression of androgen receptor and prostate-specific antigen should be examined under stringent culture conditions to establish prostatic epithelial origin. Response to growth factors and expression of their receptors facilitates further characterization of cell behavior. Cell lines immortalized by human papillomaviruses (HPVs) are of special interest because HPVs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV-18 immortalized cells with the ras oncogene provides cell systems for investigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinoma or resulted from immortalization with Simian virus 40 (SV40) or HPV, or was transformed in vitro by oncogenes. Comparisons of these characteristics should facilitate elucidation of the mechanisms involved in the initiation, promotion, and progression of prostate cancer. These cell lines will further serve as useful models for investigating tumor progression, invasion, metastasis, new therapeutic strategies, drug resistance, and its reversal and chemoprevention. The nontumorigenic cell lines were discussed in Part 1 [1]. This review summarizes the characteristics of several currently available tumorigenic, adult human prostatic epithelial cell lines.
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PMID:Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications Part 2. Tumorigenic cell lines. 901 37

This is Part 3 of a three-part review. It deals with the possible role of oncogenes and suppressor genes in human prostate carcinoma as well applications of nontumorigenic and tumorigenic human prostate cell lines described in Parts 1 and 2 [1,2]. Several immortalized and malignant adult human prostatic epithelial cell lines have recently been developed. The three most widely used carcinoma cell lines, DU-145, PC-3, and LNCaP, developed between 1977 and 1980, have greatly contributed to our present understanding of prostate cancer. Before a cell line can be accepted as having prostatic epithelial origin, some basic characteristics must be established. Expression of specific cytokeratins but absence of desmin and factor VIII should be first determined to establish epithelial origin. Responsiveness to androgens and expression of androgen receptor and prostate-specific antigen should be examined under stringent culture conditions to establish prostatic epithelial origin. Response to growth factors and expression of their receptors facilitates further characterization of cell behavior. Cell lines immortalized by human papillomaviruses (HPVs) are of special interest because HPVs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV-18 immortalized cells with the ras oncogene provides cell systems for investigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinoma or resulted from immortalization with simian virus 40 (SV40) or HPV, or was transformed in vitro by oncogenes. Comparisons of these characteristics should facilitate elucidation of the mechanisms involved in initiation, promotion and progression of prostate cancer. These cell lines will further serve as useful models for investigating tumor progression, invasion, metastasis, new therapeutic strategies, drug resistance and its reversal and chemoprevention. This review summarizes some applications of the currently available immortalized, non-tumorigenic as well as the tumorigenic adult human prostatic epithelial cell lines.
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PMID:Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications. Part 3. Oncogenes, suppressor genes, and applications. 905 Nov 52

Extensive scientific literature data point to reciprocal interactions between prostate stromal cells and prostate cancer cells that likely regulate tumor progression. To investigate whether these intratumoral-reactive stromal cells in human prostate cancer are predictive of survival, tumor stroma volume and specific stroma markers were quantitated by using tissue microarrays (index tumors of 847 patients), and the results were analyzed relative to the recurrence-free survival data set for these patients. Tumor tissue was evaluated with Masson's trichrome stains and by immunohistochemistry with antibody probes to smooth muscle alpha-actin, desmin, vimentin, pro-collagen type I, and calponin. The relative volume of intratumor stroma (5% stroma, grade 0; 5-15%, grade 1; 15-50%, grade 2; >50%, grade 3) and the expression index of stromal marker (staining intensity grade x percentage of positive cells per field) were quantitated and analyzed. Interpretable data were obtained from 545 patients. Statistical analysis of the survival data set showed that the volume of reactive stroma in the tumor was a significant predictor of disease-free survival. Stroma volume was most optimal as an independent predictor in tumors containing stroma, defined as Gleason 7 and lower grades. Of interest, tumors with either little to no stroma or tumors with abundant stroma each showed reduced recurrence-free survival. For specific stromal markers, reduced desmin and smooth muscle alpha-actin were hallmarks of cancer-associated reactive stroma relative to normal fibromuscular stroma. Quantitative analysis of desmin and smooth muscle alpha-actin expression showed both to be significant and independent predictors of recurrence-free survival. This is the first study to demonstrate that nonepithelial-reactive stroma elements in prostate cancer tumors can be used as prognostic indicators. These data also add to the concept that tumors are not purely epithelial and the tumor-reactive stroma must be considered an important biological component of the cancer.
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PMID:Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer. 1458 50

The transgenic adenocarcinoma mouse prostate (TRAMP) model, designed for researching human prostatic cancer, was genetically engineered to harbor a transgene composed of the simian virus 40 Large-T/small-t antigen promoted by the rat probasin gene. In addition to prostatic neoplasms, the TRAMP mouse develops tumors in the seminal vesicles. This study was conducted to evaluate the pathology and histogenesis of TRAMP seminal vesicle neoplasms. Tissues of accessory sex organs harvested from 72 TRAMP mice of various ages (11-40 weeks of age) were fixed in neutral buffered formalin and stained with hematoxylin and eosin, desmin, 5-bromo-2'-deoxyuridine (BrdU, treated animals only), and SV40 Large-T antigen (SV40-Tag). In the seminal vesicles, we found neoplastic stromal cells that emerged multicentrically just beneath the epithelium, densely packed between the epithelium and the smooth muscle layer. These stromal cells frequently exhibited mitotic figures and showed BrdU incorporation and SV40-Tag protein expression in the nuclei and immunopositivity for desmin. The proliferative mesenchymal cells were lined by cuboidal to columnar epithelium. Some of the larger papillary, polypoid lesions exhibited a phyllodes pattern resembling that seen in mixed epithelial-stromal tumors of the breast, prostate, and seminal vesicles of humans. Although the epithelium was negative for SV40-Tag and showed only occasional incorporation of BrdU, it clearly participated in the biphasic proliferation, forming papillary, cystic, and tubuloglandular structures. No conclusive evidence of malignancy (invasion or metastasis) was identified. Our recommended diagnosis of this lesion in the seminal vesicles is epithelial-stromal tumor.
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PMID:Epithelial-stromal tumor of the seminal vesicles in the transgenic adenocarcinoma mouse prostate model. 1587 76

Estrogens have been implicated to play certain but yet undefined roles in the normal and neoplastic growth of prostate gland. Studies of perinatal exposure in rodents demonstrate that effects of perinatal estrogenization are permanent and carcinogenic in prostate gland. In the Noble (Nb) rat model, prostatic dysplasia and neoplastic lesions can be induced by a chronic treatment with both testosterone and estrogen at adulthood. However, by this conventional protocol, neoplastic lesions are mostly confined to the lateral (LP) and ventral (VP) prostates, while gross prostatic tumors are rarely induced. Based on these two experimental models, we developed a modified treatment protocol for the enhancement of prostate cancer induction in Nb rat model by combining neonatal estrogen exposure of male offspring followed by the hormonal treatment at adulthood (NeoE + T-E2). Using this modified protocol, we were able to induce more extensive development of neoplastic lesions in all three prostatic lobes and also gross tumors at relatively high incidence within 6-9 months. Western blottings and immunohistochemistry showed that ERalpha expression was increased in the hypertrophic peri-acinar and -ductal smooth muscle cells while ERbeta and AR expressions are markedly decreased in dysplastic and neoplastic lesions in NeoE + T-E2-treated prostates. Immunohistochemistry showed that expression of three tumor suppressors (BRCA2, PTEN, and Rap1) and tubulin-alpha are markedly decreased in dysplastic and neoplastic lesions. In addition, loss of expression of smooth muscle differentiation markers (desmin, alpha-actin, and vinculin) and defects of basement membranes were also seen in the reactive stroma. These results suggest that exposure to high levels of estrogens, either endogenous or exogenous, in early life could play a role in the development of prostate cancer in later life.
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PMID:Enhanced induction of prostatic dysplasia and carcinoma in Noble rat model by combination of neonatal estrogen exposure and hormonal treatments at adulthood. 1627 25

Prostate cancer is one of the four most common cancers in the United States, affecting one of six men. Increased serum levels of androgens and IGF-I are associated with an augmented risk of prostate cancer. Dihydrotestosterone (DHT) and testosterone (T) stimulate prostate cancer cell growth, development, and function, whereas the effects of DHT and T in prostate stromal cells, and of dehydroepiandrosterone (DHEA) in prostate cancer or stromal cells, are uncertain. We investigated the actions of DHT, T, DHEA, and estradiol (E2) on insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor (R), IGF-binding protein (IGFBP)-2, IGFBP-3, and IGFBP-5 in primary cultures of human prostatic stromal cells by assessing cell proliferation, mRNA expression, and protein secretion by MTT growth assay, quantitative real-time PCR, and ELISA, respectively. DHT and T each increased IGF-I (7-fold) and decreased IGFBP-3 (2-fold) mRNA expression and protein secretion in a dose- and time-dependent manner and increased IGFBP-2 (2-fold) mRNA in a dose- and time-dependent manner. DHEA and E2 did not significantly alter these measures. Flutamide abolished the DHT-modulated increases in IGF-I and IGFBP-2, suggesting that the influences of DHT and T on these measures were androgen receptor mediated. None of the four steroids significantly affected IGF-IR, IGF-II, or IGFBP-5 mRNA levels or stromal cell proliferation. The effects of DHT on IGF-I, IGFBP-2, and IGFBP-3 were more pronounced in stromal cultures that did not express desmin. These data suggest that DHT and T promote prostate growth partly via modulation of the stromal cell IGF axis, with potential paracrine effects on prostate epithelial cells.
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PMID:DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells. 1636 82

Inflammatory myofibroblastic tumor (IMT) of the urinary tract, also termed postoperative spindle cell nodule, inflammatory pseudotumor, and pseudosarcomatous fibromyxoid tumor, is rare and in the past was believed to reflect diverse entities. We reviewed a series of 46 IMTs arising in the ureter, bladder, and prostate, derived primarily from a large consultation practice. There were 30 male and 16 females aged 3 to 89 years (mean 53.6). Lesions were 1.2 to 12 cm (mean 4.2). There was a history of recent prior instrumentation in 8 cases. Morphology was similar to that previously described for IMT occurring in this region, with the exception of 1 case that focally appeared sarcomatous. Polypoid cystitis coexisted in 5 patients (11%). Mitoses were typically scant (0 to 20/10 hpf, mean 1). Necrosis was seen in 14 (30%) cases. Invasion of the muscularis propria was documented in 19 (41%). By immunohistochemistry (IHC), lesions at least focally expressed anaplastic lymphoma kinase (ALK) (20/35, 57%), AE1/3 (25/34, 73%), CAM5.2 (10/15, 67%), CK18 (6/6, 100%), actin (23/25, 92%), desmin (15/19, 79%), calponin (6/7, 86%), caldesmon (4/7, 57%, rare cells), p53 (10/13, 77%), and most lacked S100 (0/14), CD34 (0/13), CD117 (2/13, 15%), CD21 (0/5), and CD23 (0/3). ALK gene alterations were detected by fluorescence in situ hybridization (FISH) in 13/18 (72%) tested cases, including 2 with prior instrumentation; 13/18 (72%) showed agreement between FISH ALK results and ALK protein results by IHC. Most bladder IMTs were managed locally, but partial cystectomy was performed as the initial management in 7 cases and cystectomy in 1 (1 IMT was initially misinterpreted as carcinoma, 1 IMT was found incidentally as a separate lesion in a cystectomy specimen performed for urothelial carcinoma). Follow-up was available in 32 cases (range 3 to 120 mo; mean 33; median 24). There were 10 patients with recurrences (2 with 2 recurrences). Recurrences were unassociated with muscle invasion or with ALK alterations. In 2 cases, tumors of the urinary tract (TURs) showing IMT preceded (1 and 2 mo, respectively) TURs showing sarcomatoid carcinoma with high-grade invasive urothelial carcinoma accompanied with separate fragments of IMT. Even on re-review the IMT in these 2 cases were morphologically indistinguishable from other cases of IMT, with FISH demonstrating ALK alterations in the IMT areas in one of them. Both these patients died of their carcinomas. Lastly, there was 1 tumor with many morphological features of IMT and an ALK rearrangement, yet overtly sarcomatous. This case arose postirradiation for prostate cancer 4 years before the development of the lesion, with tumor recurrence at 4 months and death from intra-abdominal metastatic disease at 9 months. In summary, urinary tract IMTs are rare and share many features with counterparts in other sites, displaying similar morphology and immunogenotypic features whether de novo or postinstrumentation. Typical IMTs can be locally aggressive, sometimes requiring radical surgical resection, but none of our typical cases metastasized, although they can rarely arise contemporaneously with sarcomatoid urothelial carcinomas. For these reasons, close follow-up is warranted.
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PMID:Inflammatory myofibroblastic tumors of the urinary tract: a clinicopathologic study of 46 cases, including a malignant example inflammatory fibrosarcoma and a subset associated with high-grade urothelial carcinoma. 1712 5

Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin alpha2beta1(hi) and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 microg/ml insulin (DMEM+10% FBS+Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including CK5/14, CD44, p63 and cytokeratin 18 (CK18); as well as the mesenchymal cell markers, vimentin, desmin; the neuron and neuroendocrine cell marker, chromogranin A. Furthermore the RC170 N/h/clone 7 cells differentiated into multi tissues when transplanted into the sub-renal capsule and subcutaneously of NOD-SCID mice. The results indicate that RC170N/h/clone 7 cells retain the properties of multipotent stem cells and will be useful as a novel cell model for studying the mechanisms of human prostate stem cell differentiation and transformation.
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PMID:Telomerase-immortalized non-malignant human prostate epithelial cells retain the properties of multipotent stem cells. 1790 May 65


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