scholarly journals A Novel Subset of Human tumors that Simultaneously Overexpress Multiple E2F-responsive Genes Found in Breast, Ovarian, and Prostate Cancers

2014 ◽  
Vol 13s5 ◽  
pp. CIN.S14062 ◽  
Author(s):  
Stanley E. Shackney ◽  
Salim Akhter Chowdhury ◽  
Russell Schwartz
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Cell Cycle Progression ◽  
Multiple Organ ◽  
Serous Ovarian Cancer ◽  
Cycle Progression ◽  
Gene Expression Microarray Data ◽  
Cancer Types ◽  
Prostate Cancers

Reasoning that overexpression of multiple E2F-responsive genes might be a useful marker for RB1 dysfunction, we compiled a list of E2F-responsive genes from the literature and evaluated their expression in publicly available gene expression microarray data of patients with breast cancer, serous ovarian cancer, and prostate cancer. In breast cancer, a group of tumors was identified, each of which simultaneously overexpressed multiple E2F-responsive genes. Seventy percent of these genes were concerned with cell cycle progression, DNA repair, or mitosis. These E2F-responsive gene overexpressing (ERGO) tumors frequently exhibited additional evidence of Rb/E2F axis dysfunction, were mostly triple negative, and preferentially overexpressed multiple basal cytokeratins, suggesting that they overlapped substantially with the basal-like tumor subset. ERGO tumors were also identified in serous ovarian cancer and prostate cancer. In these cancer types, there was no evidence for a tumor subset comparable to the breast cancer basal-like subset. A core group of about 30 E2F-responsive genes were overexpressed in all three cancer types. Thus, it appears that disorders of the Rb/E2F axis can arise at multiple organ sites and produce tumors that simultaneously overexpress multiple E2F-responsive genes.

Stratification of risk for patients with prostate cancer at biopsy using CCP score.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 127-127 ◽  
Author(s):  
Neal D. Shore ◽  
Brian Abbott ◽  
Raoul S. Concepcion ◽  
Daniel Saltzstein ◽  
Rajesh R. Kaldate ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Risk Assessment ◽  
Gleason Score ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Clinical Stage ◽  
Cycle Progression ◽  
Cancer Aggressiveness ◽  
Prostate Cancers

127 Background: In the US, most prostate cancers are treated with surgery or radiation, despite many having low malignant potential. If low cancer progression risk can be established, some men can be spared treatment. PSA, Gleason score and clinical stage work well for population risk assessment but lack precision for individuals. Molecular analysis can refine risk assessment as demonstrated by a cell cycle progression score (CCP) predictive of prostate cancer aggressiveness in 4 separate cohorts. In these studies, CCP typically ranged from −2 to +3 with each 1−unit increase corresponding to approximately a doubling of risk. We characterized the CCP distribution using recent samples from a typical US urology multi−centered clinical setting and determined the analytic success rate of the assay. Methods: Formalin fixed, prostate biopsy tissue from 300 patients diagnosed with adenocarcinoma within the last 12 months was analyzed. CCP is calculated by measuring the relative RNA expression of 31 cell cycle progression genes. Patients were recruited from 15 geographically diverse community urology practices. Results: CCP could be measured for 98% of samples (294/300). This study showed a normal distribution for the CCP ranging from −2 to 3.2 (median = −0.3, SD=0.92). There was little correlation of CCP with PSA, age, or body mass index. Correlation with Gleason score was similar to those in prior studies (r=0.494). A relative classification of cancer aggressiveness based on CCP of ~ 1200 patients from multiple cohorts has been developed. The 294 evaluable patients were cross−classified by AUA risk and cancer aggressiveness (see table). CCP further stratified patients within each AUA risk classification. Conclusions: CCP is a novel assay that can facilitate risk stratification for men with prostate adenocarcinoma. [Table: see text]

1955-P: GLP-1R Activation Attenuates Prostate Cancer Growth via Inhibiting Cell Cycle Progression

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1955-P
Author(s):  
TORU SHIGEOKA ◽  
TAKASHI NOMIYAMA ◽  
TAKAKO KAWANAMI ◽  
YURIKO HAMAGUCHI ◽  
TOMOKO TANAKA ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cancer Growth ◽  
Cycle Progression

scholarly journals CBP/p300: Critical Co-Activators for Nuclear Steroid Hormone Receptors and Emerging Therapeutic Targets in Prostate and Breast Cancers

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2872
Author(s):  
Aaron R. Waddell ◽  
Haojie Huang ◽  
Daiqing Liao
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Tumor Growth ◽  
Signaling Pathways ◽  
Cell Cycle Progression ◽  
Hormone Receptors ◽  
Steroid Hormone Receptors ◽  
Breast Cancers ◽  
Creb Binding Protein ◽  
Breast And Prostate Cancer

The CREB-binding protein (CBP) and p300 are two paralogous lysine acetyltransferases (KATs) that were discovered in the 1980s–1990s. Since their discovery, CBP/p300 have emerged as important regulatory proteins due to their ability to acetylate histone and non-histone proteins to modulate transcription. Work in the last 20 years has firmly established CBP/p300 as critical regulators for nuclear hormone signaling pathways, which drive tumor growth in several cancer types. Indeed, CBP/p300 are critical co-activators for the androgen receptor (AR) and estrogen receptor (ER) signaling in prostate and breast cancer, respectively. The AR and ER are stimulated by sex hormones and function as transcription factors to regulate genes involved in cell cycle progression, metabolism, and other cellular functions that contribute to oncogenesis. Recent structural studies of the AR/p300 and ER/p300 complexes have provided critical insights into the mechanism by which p300 interacts with and activates AR- and ER-mediated transcription. Breast and prostate cancer rank the first and forth respectively in cancer diagnoses worldwide and effective treatments are urgently needed. Recent efforts have identified specific and potent CBP/p300 inhibitors that target the acetyltransferase activity and the acetytllysine-binding bromodomain (BD) of CBP/p300. These compounds inhibit AR signaling and tumor growth in prostate cancer. CBP/p300 inhibitors may also be applicable for treating breast and other hormone-dependent cancers. Here we provide an in-depth account of the critical roles of CBP/p300 in regulating the AR and ER signaling pathways and discuss the potential of CBP/p300 inhibitors for treating prostate and breast cancer.

Sign in / Sign up

Export Citation Format

Share Document