scholarly journals A comprehensive analysis of polymorphic variants in steroid hormone and insulin-like growth factor-1 metabolism and risk of in situ breast cancer: Results from the Breast and Prostate Cancer Cohort Consortium

2017 ◽  
Vol 142 (6) ◽  
pp. 1182-1188
Author(s):  
Myrto Barrdahl ◽  
Federico Canzian ◽  
Mia M. Gaudet ◽  
Susan M. Gapstur ◽  
Antonia Trichopoulou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Growth Factor ◽  
Steroid Hormone ◽  
Comprehensive Analysis ◽  
Insulin Like Growth Factor ◽  
Polymorphic Variants ◽  
Breast And Prostate Cancer ◽  
In Situ Breast Cancer

Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells

2004 ◽  
Vol 11 (4) ◽  
pp. 793-814 ◽  
Author(s):  
H E Jones ◽  
L Goddard ◽  
J M W Gee ◽  
S Hiscox ◽  
M Rubini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Growth Factor ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Line ◽  
Acquired Resistance ◽  
Continuous Exposure ◽  
Prostate Cancer Cells ◽  
Breast And Prostate Cancer

De novo and acquired resistance to the anti-tumour drug gefitinib (ZD1839; Iressa), a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been reported. We have determined whether signalling through the IGF-I receptor (IGF-1R) pathway plays a role in the gefitinib-acquired resistance phenotype. Continuous exposure of EGFR-positive MCF-7-derived tamoxifen resistant breast cancer cells (TAM-R) to 1 μM gefitinib resulted in a sustained growth inhibition (90%) for 4 months before the surviving cells resumed proliferation. A stable gefitinib-resistant subline (TAM/TKI-R) was established after a further 2 months and this showed no detectable basal phosphorylated EGFR activity. Compared with the parental TAM-R cells, the TAM/ TKI-R cells demonstrated (a) elevated levels of activated IGF-1R, AKT and protein kinase C (PKC)δ, (b) an increased sensitivity to growth inhibition by the IGF-1R TKI AG1024 and (c) an increased migratory capacity that was reduced by AG1024 treatment. Similarly, the EGFR-positive androgen-independent human prostate cancer cell line DU145 was also continuously challenged with 1 μM gefitinib and, although substantial growth inhibition (60%) was seen initially, a gefitinib-resistant variant (DU145/TKI-R) developed after 3 months. Like their breast cancer counterparts, the DU145/TKI-R cells showed increases in the levels of components of the IGF-1R signalling pathway and an elevated sensitivity to growth inhibition by AG1024 compared with the parent DU145 cell line. Additionally, DU145/TKI-R cell migration was also decreased by this inhibitor. We have therefore concluded that in breast and prostate cancer cells acquired resistance to gefitinib is associated with increased signalling via the IGF-1R pathway, which also plays a role in the invasive capacity of the gefitinib-resistant phenotype.

Insulin-Like Growth Factor I Polymorphisms in Breast Cancer

2002 ◽  
Author(s):  
Rebecca J. Cleveland ◽  
Marilie D. Gammon ◽  
Ralph S. Baric
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Growth Factor I

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