Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0376358 (
prostate cancer
)
59,338
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The CAG repeat within exon 1 of the androgen receptor (AR) has been associated with the development of
prostate cancer
. The shorter number of glutamine residues in the protein has been associated with a higher transcriptional activity of the AR and increased relative risk for
prostate cancer
. In an attempt to identify differentially expressed genes in
prostate cancer
in relation to AR CAG repeat length variation, in this study we used total mRNA from normal and tumor tissues from 2
prostate cancer
patients with AR alleles containing 19 and 26 CAG repeats to perform differential-display RT-PCR analysis. We were able to identify 48 different transcripts that showed homology to several known genes associated with different biological pathways. Among the differentially expressed genes,
ATRX
and SFRP1 were further validated by quantitative RT-PCR. The transcripts of both
ATRX
and SFRP1 genes proved to be down-regulated in most of the prostate tumors analyzed by quantitative RT-PCR. Hypermethylation of the promoter region of the SFRP1 gene was found in 17.5% (7/40) of the cases analyzed and was associated with the loss of SFRP1 expression (p=0.014). The differentially expressed genes identified in this study are implicated in several cellular pathways that, when up- or down-regulated, might play a role in the tumorigenic process of the prostate.
...
PMID:Identification of differentially expressed genes in prostatic epithelium in relation to androgen receptor CAG repeat length. 1684 12
A key hallmark of cancer, unlimited replication, requires cancer cells to evade both replicative senescence and potentially lethal chromosomal instability induced by telomere dysfunction. The majority of cancers overcome these critical barriers by upregulating telomerase, a telomere-specific reverse transcriptase. However, a subset of cancers maintains telomere lengths by the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. The presence of ALT is strongly associated with recurrent cancer-specific somatic inactivating mutations in the
ATRX
-DAXX chromatin-remodeling complex. Here, we generate an ALT-positive adenocarcinoma cell line following functional inactivation of
ATRX
and telomerase in a telomerase-positive adenocarcinoma cell line. Inactivating mutations in
ATRX
were introduced using CRISPR-cas9 nickase into two
prostate cancer
cell lines, LAPC-4 (derived from a lymph node metastasis) and CWR22Rv1 (sourced from a xenograft established from a primary
prostate cancer
). In LAPC-4, but not CWR22Rv1, abolishing
ATRX
was sufficient to induce multiple ALT-associated hallmarks, including the presence of ALT-associated promyelocytic leukemia bodies (APB), extrachromosomal telomere C-circles, and dramatic telomere length heterogeneity. However, telomerase activity was still present in these
ATRX
KO
cells. Telomerase activity was subsequently crippled in these LAPC-4
ATRX
KO
cells by introducing mutations in the
TERC
locus, the essential RNA component of telomerase. These LAPC-4
ATRX
KO
TERC
mut
cells continued to proliferate long-term and retained ALT-associated hallmarks, thereby demonstrating their reliance on the ALT mechanism for telomere maintenance. IMPLICATIONS: These
prostate cancer
cell line models provide a unique system to explore the distinct molecular alterations that occur upon induction of ALT, and may be useful tools to screen for ALT-specific therapies.
...
PMID:Functional Loss of
ATRX
and
TERC
Activates Alternative Lengthening of Telomeres (ALT) in LAPC4 Prostate Cancer Cells. 3161 8
