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R W deVere White

Publications and source records attributed to R W deVere White.

At least 19 recordsLinked to original sources
PubMed2001

BCL2 antisense transcripts decrease intracellular Bcl2 expression and sensitize LNCaP prostate cancer cells to apoptosis-inducing agents.

Prostate cancer (CaP) is the most commonly diagnosed cancer of aging men and the second leading cause of male cancer death in the United States. At present, no effective therapy is available for treating hormone independent CaP. Since Bcl2 is believed to play a role in protecting CaP cells from apoptosis, we investigated the effects of down-regulating Bcl2 expression on CaP cells. Genetically engineered LNCaP sublines were established by stably transfecting LNCaP cells with BCL2 antisense (BCL2-AS) transcript-expressing plasmids. Western blotting analysis showed that intracellular Bcl2 protein was decreased by 50-60% in BCL2-AS-transfected LNCaP cells. Expression of the antisense transcripts resulted in 50% growth inhibition of LNCaP cells in response to androgen withdrawal and markedly sensitized these cells to Adriamycin-induced apoptosis. These results suggest that down-regulation of Bcl2 protein using BCL2-AS transcripts could be exploited for improved treatment of advanced CaP.

Adenocarcinoma↗
PubMed2001

Differences in gene expression in muscle-invasive bladder cancer: a comparison of Italian and American patients.

OBJECTIVE: To seek differences in gene expression in the primary muscle-invasive bladder cancers of two cohorts of patients having different survival rates. An Italian group treated by transurethral resection of the bladder tumor (TURBT) and neo-adjuvant chemotherapy using methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) followed by TURBT, partial cystectomy or radical cystectomy (75% 3-year survival) was compared to an American cohort treated by radical cystectomy (51% 3-year survival). METHODS: Immunohistochemistry was used to examine the protein expression levels of three genes that act at the G1/S cell cycle checkpoint, p53, p21/waf-1/cip1 (a downstream effector gene in the p53 pathway) and Rb, plus a major inhibitor of apoptosis, Bcl-2. RESULTS: For the bladder cancers of the Italian patient cohort, there was a significantly higher rate of p53 immunopositivity (93 vs. 63%, p = 0.002) and a significantly lower rate of Rb loss (25 vs. 54%, p = 0.009). In bivariate analysis, 72% of Italian tumors were immunopositive for both p53 and p21 (p53+/p21+) vs. 49% for the American tumors. The subset of Italian patients with p53+/p21+ tumors were more frequently disease-free (stage pT0) following chemotherapy and were less likely to fail therapy than those with p53+/p21- tumors (p = 0.0357). Loss of Rb staining was associated with a decreased 5-year survival in the Italian, but not in the American patients. CONCLUSIONS: (1) Significant differences in the expression of the p53, p21 and Rb genes were found between the 2 groups of patients. (2) Italian patients with p53+/p21+ tumors had significantly lower recurrence rates after TURBT and chemotherapy than those having p53+/p21- tumors. (3) Absence of p21 immunopositivity in the Italian tumors may identify alterations in the p53 pathway that predict poor outcome.

Gene Expression Regulation, Neoplastic↗
PubMed2000

Acute toxicity of three-dimensional conformal radiotherapy in prostate cancer patients eligible for implant monotherapy.

PURPOSE: To assess the acute toxicity of three-dimensional conformal radiotherapy (3D-CRT) in prostate cancer patients eligible for implant monotherapy. METHODS AND MATERIALS: Between December 1991 and June 1998, 198 prostate cancer patients were treated with 3D-CRT at the University of California Davis Medical Center. Fifty-two of these patients had a prostate-specific antigen (PSA) level </= 10.0 ng/ml, Gleason score </= 6, and a 1997 AJCC clinical stage T1bN0-T2bN0. Eleven (21%) patients received radiotherapy to the prostate and seminal vesicles; the remaining patients were treated to the prostate only. The 3D-CRT treatment planning guidelines in Radiation Therapy Oncology Group (RTOG) 9406 were followed after 1994 (similar treatment planning was used before the protocol became available). Typically, 4 oblique and 2 lateral fields were treated. All patients were seen at least weekly while under treatment, 1 month postirradiation and then every 3 months. Total radiation doses ranged from 66.0-79.2 Gy, with a median dose of 73.8 Gy in 41 fractions over 8 weeks. Acute toxicity is described according to the RTOG acute toxicity scoring system. RESULTS: Overall, 3D-CRT was well-tolerated: 29% of patients experienced RTOG Grade 1 and 27% experienced Grade 2 acute lower gastrointestinal (GI) toxicity. Forty percent and 33% of patients experienced Grade 1 and 2 acute genitourinary (GU) toxicity, respectively. As expected, more acute morbidity, especially GI, was observed with a larger clinical target volume (prostate and seminal vesicles versus prostate only; p = 0. 05). Neoadjuvant hormonal therapy did not increase the incidence or severity of radiation-induced side effects. No acute toxicity >/= Grade 3, e.g., hourly nocturia, gross hematuria, diarrhea requiring parenteral support, narcotics for pain control, or catheterization for acute urinary retention, was observed. CONCLUSION: Although relatively high doses of radiation are delivered to prostate cancers with 3D-CRT compared with conventional radiotherapy, 3D-CRT is surprisingly well-tolerated. No patients in the cohort eligible for implant monotherapy experienced acute toxicity >/= Grade 3.

Acute Disease↗
PubMed2000

Phase I/II study of paclitaxel, carboplatin, and methotrexate in advanced transitional cell carcinoma: a well-tolerated regimen with activity independent of p53 mutation.

OBJECTIVES: To evaluate the feasibility and activity of paclitaxel, carboplatin, and methotrexate in advanced transitional cell carcinoma (TCC) of the urothelium and to relate the activity of this combination to the mutational status of p53. METHODS: In the Phase I portion, paclitaxel 200 mg/m(2) (3-hour infusion), carboplatin dosed to an area under the curve (AUC) of 6 mg/mL. min, and methotrexate 10 mg/m(2), increasing in 10-mg/m(2) increments, were administered on day 1 and every 21 days thereafter with granulocyte colony-stimulating factor (G-CSF) and leucovorin support. Subsequently, a Phase II study was initiated in which the carboplatin dose was lowered to an AUC of 5 to allow treatment without G-CSF. p53 expression was evaluated using immunohistochemistry. RESULTS: Thirty-three patients were accrued. Median age was 66 years. No dose-limiting toxicities were seen in the Phase I portion despite escalation of the methotrexate to 60 mg/m(2). Principal toxicities were myelosuppression and neuropathy. The overall response rate (Phase I and II) was 56% (95% confidence interval 38% to 74%). Median survival was 15.5 months; 88% of patients overexpressed p53 at the primary site. CONCLUSIONS: Paclitaxel, carboplatin, and methotrexate were well tolerated and active in advanced TCC. The high response rate to this regimen despite frequent p53 mutation is consistent with the p53-independent mechanism of paclitaxel. Whether this regimen is superior to methotrexate/vinblastine/doxorubicin/cisplatin, other paclitaxel-based regimens, or to paclitaxel alone will require comparative trials.

Aged↗
PubMed2000

The prognostic significance of S-phase analysis in stage Ta/T1 bladder cancer. A Southwest Oncology Group Study.

OBJECTIVES: An intergroup study (SWOG 8795) comparing two forms of adjunctive therapy (immuno and chemo), bacillus Calmette-Guerin (BCG) and mitomycin C (MMC), furnished preregistration index tumors for 244 patients with superficial, papillary stage Ta/T1 TCC. These were examined by flow cytometry to learn whether DNA ploidy or proliferation (low vs high S-phase fraction (SPF) helped to predict disease recurrence or progression. METHODS: Cell cycle analysis using commercially available (Multicycle) programs was performed on 249 Ta/T1 bladder cancers. Tumor grade, available for 223 cases, was assigned by a single study pathologist. The SWOG statistical office reviewed follow-up information and other data and performed statistical analysis. RESULTS: Disease recurrence occurred in half the cases studied. The most parsimonious model predictive of recurrence included only treatment arm and tumor grade, with the MMC arm and tumor grade greater than I indicating worse prognosis (p = 0. 014). Neither ploidy nor SPF predicted recurrence-free survival or contributed prognostic information that was additive to tumor grade. Within 5 years of follow-up, disease progression or death from bladder cancer occurred for 29/223 (13%) of patients. The most parsimonious model for progression-free survival included only grade greater than I (p<0.001) and high SPF (p = 0.029) (relative risk: tumor grade, 4.3, high SPF, 1.9). CONCLUSIONS: Knowledge of tumor proliferation (low versus high SPF) contributes prognostic information about tumor progression that is additive to tumor grade.

Cell Division↗
PubMed1999

Use of a yeast assay to detect functional alterations in p53 in prostate cancer: review and future directions.

BACKGROUND: While many studies have suggested that p53 mutations are common in human cancers, the functional activity of these mutant alleles has not yet been fully addressed. We believe that information about the functional status of individual p53 mutants will prove to be important for a better understanding of the role of p53 in tumor development and progression. Ultimately, this information could also influence treatment decisions for individual cancer patients. METHODS: A recently developed yeast functional assay can be used to assess the transactivational activity of p53 mutants. Furthermore, this assay is more sensitive than single strand conformational polymorphism (SSCP) for detection of p53 mutations. In this review, we summarize the mechanism of this new technique and describe its applications in cancer research, with an emphasis on prostate cancer. RESULTS: The use of the yeast functional assay provides a simple, sensitive, and reproducible method for detecting p53 mutations and for determining the transactivational activity and dominant-negative role of individual p53 mutants. CONCLUSIONS: This method may be adapted to analyze other transcriptional factors, including the human androgen receptor.

Biological Assay↗
PubMed1999

Future prospects in prostate cancer.

BACKGROUND: Prostate cancer has displayed an increase in incidence unparalleled by any other tumor in the last two decades, with a steady, more gradual increase in mortality rate. Current curative strategies are focused on the detection and treatment of early-stage (T1-2 N0 M0), clinically significant tumors. METHODS: To this aim, refinement of surgical approaches, with appropriate adjuvant therapies, will ensure more complete cancer control, while minimizing associated morbidity. New delivery systems for radiotherapy, as well as other energy sources, are evolving, while a number of promising pharmacological agents, including angiogenesis inhibitors and drugs which alter signal transduction pathways, are currently under investigation. Early detection is also being facilitated by a more widespread implementation of screening programs. Advances in tumor markers, and imaging and biopsy techniques, will allow more accurate preoperative staging. These, coupled with improvements in prognostic markers, aid the physician and patient alike in deciding on the suitability of treatment options with better estimation of outcome. Perhaps the most exciting developments in prostate cancer will come from knowledge of the molecular mechanisms underlying carcinogenesis. The potential for the development of diagnostic and therapeutic tools is immense. The efficacy of treatment can be studied at a molecular level, and strategies for preventing or slowing the development of malignancy can be formulated. RESULTS AND CONCLUSIONS Application of this knowledge in the form of gene and cellular therapy and in the development of novel systemic agents is beginning to enter the realm of clinical practice, and it may be in this field that means for cure and prevention of prostate cancer will eventually be found.

Clinical Trials as Topic↗
PubMed1999

Overexpression of cyclin D1 is rare in human prostate carcinoma.

BACKGROUND: Overexpression of cyclin D1 has been documented in a number of human cancers. Increased expression of cyclin D1 can contribute to cellular transformation and abnormal proliferation. METHODS: Quantitative RT-PCR and/or Western blot analysis were used to determine the level of cyclin D1 expression in 96 human prostate tumors, 15 benign prostate hyperplasias, 4 prostate cancer cell lines, and 3 xenografts. RESULTS: Our results demonstrate that 4.2% of the prostate tumors examined overexpressed cyclin D1 transcripts. In the cell lines, expression was normal, with the exception that reduced levels of cyclin D1 transcript and protein were observed in the DU145 cell line, as expected from cells with mutant RB. Normal levels of cyclin D1 were found in all xenograft tumors and BPH specimens examined. CONCLUSIONS: These data show that overexpression of cyclin D1 occurs rarely in human prostate tumors. However, when overexpression of cyclin D1 does occur, it may identify a subset of tumors with a different molecular biology.

Blotting, Southern↗
PubMed1998

Very frequent p53 mutations in metastatic prostate carcinoma and in matched primary tumors.

BACKGROUND: The frequency of mutant p53 in bone marrow metastases of patients with carcinoma of the prostate (CaP) and in matched sets of metastatic and primary lesions from the same patients was investigated. The data were examined in relation to prior treatment with androgen ablation (AA) therapy and were compared with the frequency of mutant p53 reported for primary CaP. METHODS: Seventeen patients with M1b (bone metastasis: TNM Stage IV) CaP had either unilateral or bilateral bone marrow biopsies taken for these studies. Specimens were divided and the outer one-third examined histologically to confirm the presence of CaP cells. Immunohistochemical (IHC) staining for accumulated p53 protein was performed by an antibody cocktail technique. RNA was extracted from the remaining portion of the biopsy, and p53 transcripts were amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) and screened for base sequence changes in the exon 4-11 region using nonisotopic single-strand conformation polymorphism (SSCP) analysis and direct DNA sequencing. RESULTS: Ten of 17 metastases (59%) demonstrated accumulation of p53. Six of 7 (86%) of the p53 IHC positive bone marrow samples contained RT-PCR-SSCP abnormalities, as did 2 of 3 IHC negative samples. Overall, 12 of 17 metastases (71%) contained mutant p53. Four of 7 biopsies (57%) retrieved prior to AA contained mutant p53, whereas 8 of 10 post-AA biopsies (80%) contained mutant p53. One patient showed identical SSCP abnormalities in right and left iliac crest metastases after therapy, and in this patient DNA sequencing demonstrated a missense mutation at codon 126 (TAC --> GGC, Tyr --> Gly). Archival primary cancers from seven patients were retrieved. All seven were IHC positive for p53 accumulation. CONCLUSIONS: p53 mutations are associated with increased metastatic potential of CaP. Abnormalities are found at approximately twice the frequency in metastases than in unselected samples of primary CaP, whereas in matched specimens there is a high rate of consonance. Mutant p53 may contribute to systemic therapy resistance, due to increased association with post-AA CaP specimens.

Bone Marrow↗
PubMed1998

Increased RB1 abnormalities in human primary prostate cancer following combined androgen blockade.

BACKGROUND: The RB1 proliferation control pathway is a critical determinant of cell cycle progression. Abnormalities of RB1 are found in a variety of cancers, and the association with human prostate cancer (CaP) was examined here. METHODS: RNA expression levels of RB1 in CaPs were examined by RT-PCR. RNA integrity was assessed by evaluating expression of an endogenous gene standard. RESULTS: Abnormally low RB1 mRNA expression was found in 12/33 (36%) of CaPs from patients who had received combined androgen blockade (CAB) treatment. In contrast, 6/48 (13%) untreated CaPs showed abnormally low expression. This difference was statistically significant (P = 0.015). In the samples from untreated patients, a higher frequency of abnormal RB1 was found in specimens with a higher Gleason grade (P = 0.038). In addition, one untreated stage C, grade 9 specimen was found to express RB1 transcripts lacking exon 22, as determined by sequencing of DNA from the truncated transcripts. CONCLUSIONS: These findings suggest that abnormalities of RB1 may contribute to hormone-withdrawal-related survival of CaP cells.

Androgen Antagonists↗
PubMed1998

Racial differences in clinically localized prostate cancers of black and white men.

PURPOSE: Tumor grade, deoxyribonucleic acid (DNA) ploidy, proliferation, p53 and bcl-2 expression were examined in clinically localized prostate cancers of black and white American men to learn whether these features showed racial differences. MATERIALS AND METHODS: A total of 117 prostate cancers (43 black and 74 white patients) obtained at radical prostatectomy for clinically localized disease were assigned Gleason scores by a single pathologist. Enzymatically dissociated nuclei from archival prostate cancers were examined by DNA flow cytometry using propidium iodide staining and the multicycle program to remove debris and sliced nuclei and to perform cell cycle analysis. For immunostaining after microwave antigen retrieval we used a DO-1/DO-7 monoclonal antibody cocktail for p53 and the clone 124 antibody for bcl-2. RESULTS: Significantly more black than white men had Gleason score 7 tumors. The DNA ploidy distribution of Gleason 6 or less tumors was similar for both races. As anticipated, the ploidy distribution of higher grade prostate cancer in white men was more abnormal but, unexpectedly, this was not found for higher grade prostate cancer in black men. No significant racial differences were found in S phase fractions, p53 or bcl-2 immunopositivity. However, for prostate cancer in black men there was a significant association between bcl-2 immunopositivity and higher S-phase fractions. CONCLUSIONS: The aggressive prostate cancers of black men may be characterized by the 2 features of high proliferation and a block to programmed cell death.

Apoptosis↗
PubMed1997

p53 abnormalities in primary prostate cancer: single-strand conformation polymorphism analysis of complementary DNA in comparison with genomic DNA. The Cooperative Prostate Network.

BACKGROUND: The reported frequency of mutation of the p53 tumor suppressor gene (also known as TP53) in human carcinomas of the prostate has varied widely, ranging from 3% to 42%. This variability may be a consequence of tumor heterogeneity and/or the use of different methods of analysis. Since p53 mutation has been associated with clinical outcome for a number of cancer types, determination of its true frequency in primary carcinomas of the prostate is important. PURPOSE: The principal aims of this study were as follows: 1) to validate the utility of detecting p53 gene mutations by means of polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis of complementary DNA (cDNA) (synthesized from prostate tissue RNA and 2) to study the concordance of RNA- and DNA-based PCR-SSCP assays in detecting p53 mutations in individual tumor fragments. METHODS: RNA and genomic DNA were isolated by means of standard techniques from specimens of 19 carcinomas of the prostate, selected on the basis of p53 data obtained in a previous analysis of cDNA (indicating that 14 were mutant and five were wild-type). RNA was converted into cDNA by means of reverse transcription (RT); the cDNA was then amplified by means of nonisotopic (i.e., nonradioactive) PCR, and the PCR products were subjected to SSCP analysis in polyacrylamide gels (RT-PCR-SSCP analysis). Genomic DNA was examined by means of SSCP analysis of isotopically labeled (32PO4) PCR products (DNA-PCR-SSCP analysis). In both approaches, the protein coding region of the p53 gene was divided into multiple, smaller fragments for study. PCR products exhibiting abnormal migration in SSCP gels were subjected to direct nucleotide sequencing or to cloning and sequencing of multiple clones. RESULTS: RT-PCR-SSCP and DNA-PCR-SSCP identified p53 gene abnormalities in 15 of the 19 selected carcinomas, including one previously reported to be wild-type for p53. Overall, PCR-SSCP analysis identified 18 p53 fragments with abnormalities; three carcinomas showed two abnormalities each. Six (33%) of the 18 abnormalities were detected by both RT-PCR-SSCP and DNA-PCR-SSCP, 10 (56%) were detected by RT-PCR-SSCP alone, and two (11%) were detected by DNA-PCR-SSCP alone. The 18 abnormalities were caused by 20 changes in the sequence of the p53 gene; in one carcinoma, double mutations in two individual p53 exons were identified. CONCLUSIONS AND IMPLICATIONS: PCR-SSCP analysis of both RNA and DNA allows the detection of more mutations than the analysis of either alone. Some primary carcinomas of the prostate contain more than one altered p53 gene, consistent with the possibility of intratumoral heterogeneity of mutation of this gene. For comprehensive analysis of p53 mutations in carcinomas of the prostate, and perhaps in other tumor tissues, SSCP analysis of cDNA should be used in combination with SSCP analysis of genomic DNA.

DNA, Complementary↗
PubMed1997

Dehydroepiandrosterone activates mutant androgen receptors expressed in the androgen-dependent human prostate cancer xenograft CWR22 and LNCaP cells.

An androgen receptor (AR) gene mutation identified in the androgen-dependent human prostate cancer xenograft, CWR22, changed codon 874 in the ligand-binding domain (exon H) from CAT for histidine to TAT for tyrosine and abolished a restriction site for the endonuclease SfaNI. SfaNI digestion of AR exon H DNA from normal but not from prostate cancer tissue indicated H874Y is a somatic mutation that occurred before the initial tumor transplant. CWR22, an epithelial cell tumor, expresses a 9.6-kb AR mRNA similar in size to the AR mRNA in human benign prostatic hyperplasia. AR protein is present in cell nuclei by immunostaining as in other androgen-responsive tissues. Transcriptional activity of recombinant H874Y transiently expressed in CV1 cells in the presence of testosterone or dihydrotestosterone was similar to that of wild type AR. With dihydrotestosterone at a near physiological concentration (0.01 nM), H874Y and wild type AR induced 2-fold greater luciferase activity than did the LNCaP mutant AR T877A. The adrenal androgen, dehydroepiandrosterone (10 and 100 nM) with H874Y stimulated a 3- to 8-fold greater response than with wild type AR and at 100 nM the response was similar with the LNCaP mutant. H874Y, like the LNCaP cell mutant, was more responsive to estradiol and progesterone than was wild type AR. The antiandrogen hydroxyflutamide (10 nM) had greater agonist activity (4- to 7-fold) with both mutant ARs than with wild type AR. AR mutations that alter ligand specificity may influence tumor progression subsequent to androgen withdrawal by making the AR more responsive to adrenal androgens or antiandrogens.

Androgen Antagonists↗
PubMed1997

Frequent alteration of CDKN2 (p16(INK4A)/MTS1) expression in human primary prostate carcinomas.

CDKN2 (p16(INK4A)/MTS1) is found to be mutated in a variety of human tumor types. To explore the involvement of CDKN2 in prostate carcinogenesis, alterations of CDKN2 were examined in 116 human prostate tissues and cell lines and xenografts. Markedly reduced expression of CDKN2 mRNA was found in 43% (26 of 60) of untreated primary carcinomas, whereas no alteration was observed in 10 benign prostatic hyperplasias. In 17 matched sets from individual patients, 41% of cancerous tissues in contrast to 6% of noncancerous tissues expressed low levels of CDKN2 mRNA, supporting the role of CDKN2 as a tumor suppressor in prostate cancer. Alteration of CDKN2 was observed in each prostate tumor cell line, including one with a missense mutation, and in one of three xenograft tumor tissues derived from primary carcinomas. Two cell lines (PC-3 and TSU-Pr1) expressed only CDKN2 E1beta transcripts, indicating that the expression of CDKN2 E1alpha and E1beta are under separate control in the prostate. A high level of CDKN2 expression was related to abnormal RB1 in one primary tumor and in the DU145 cell line, which expressed the mutated CDKN2 allele. Analysis of genomic DNA indicated that altered CDKN2 expression in primary carcinomas of the prostate was more frequently due to down-regulation of transcription (five of seven) than deletion of the gene (two of seven). Additionally, CDKN2 mRNA was induced in nonexpressor cell lines by treatment with 5-aza-2'-deoxycytidine. This study demonstrates that alteration of CDKN2 is one of the most frequent genetic abnormalities in prostate cancer and may contribute to prostate carcinogenesis.

Adenocarcinoma↗
PubMed1996

Alterations of the retinoblastoma gene in human prostate adenocarcinoma.

The loss or mutational inactivation of the RB1 tumor suppressor gene has been implicated in the development of a diverse group of human malignancies. However, the contribution of the RB1 gene alteration to human prostatic carcinogenesis has been poorly understood. Thus far, deletion of the promoter sequence and exon 21 from one primary tumor specimen and the alterations found in the cell line DU-145, are the only cases of RB1 mutations reported in human carcinoma of the prostate. This study was designed to determine whether alterations in the structure or expression of the RB1 gene occur in human prostate carcinoma, and to determine the nature of these changes and the frequency with which they occur. One hundred twelve primary prostate tumor tissues and four metastatic lesions were obtained immediately after surgical resection. The RB1 gene was characterized in 68 tumor DNA samples using Southern analysis and the PG3.8M or H3-8 probes. Band profiles were analyzed by scanning densitometry. Sixty-three tumor DNA samples were analyzed for defects in the RB1 promoter using polymerase chain reaction (PCR) and heteroduplex analysis. Alterations in the expression of exons 1-27 were analyzed in 79 primary and four metastatic tumor RNAs using RT-PCR. Three of 68 tumors were identified to have gross rearrangement of the RB1 gene or deletion of one allele. One of four stage D tumor specimens showed truncated RT-PCR products indicating an internal deletion of RB1 transcripts. In all, 14 of 83 (17%) specimens displayed abnormally low levels of RB1 mRNA expression. Furthermore, these alterations of RB1 expression showed a correlation with increasing tumor stage and grade. These results suggest alterations of RB1 mRNA expression occur more frequently in higher stages and grades of prostate cancer and, thus, may be contributing to the malignant progression of a subset of human prostate cancer.

Adenocarcinoma↗
PubMed1996

Molecular biology of prostate cancer.

Carcinoma of the prostate (CaP) is a very prevalent tumor among men. However thus far, relatively little information is known about the molecular mechanisms involved in the development, progression and metastasis of this disease. This article reviews the current state of knowledge of five selected molecular aspects of human CaP: tumor suppressor genes, metastasis suppressor genes and related biological events (allelic loss and DNA methylation), oncogenes (including growth factors and their receptors), the anti-apoptosis gene BCL2, and the human androgen receptor gene (hAR). Alterations of these genes in structure and expression as well as the frequencies of these molecular events are discussed to synthesize an understanding of documented genetic alterations that occur in CaP and their possible relation to the biology of the disease.

Animals↗