scholarly journals Differential Posttranscriptional Regulation of Androgen Receptor Gene Expression by Androgen in Prostate and Breast Cancer Cells*

Endocrinology ◽  
1999 ◽  
Vol 140 (7) ◽  
pp. 3282-3291 ◽  
Author(s):  
Bu B. Yeap ◽  
Romano G. Krueger ◽  
Peter J. Leedman
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
S Phase ◽  
Lncap Cells ◽  
Mrna Transcription ◽  
Down Regulation

Abstract Androgens, via the androgen receptor (AR), modulate the growth and proliferation of prostate and breast cancer cells. However, the molecular mechanisms underlying the regulation of AR gene expression by androgen in these cells remain to be fully elucidated. To explore differences in AR gene expression between these hormone-responsive tumor cell types, we studied androgen-responsive LNCaP prostate cancer and AR positive MDA453 breast cancer cells. Dihydrotestosterone (DHT) 10 nm increased LNCaP cell proliferation and the proportion of LNCaP cells in S-phase of the cell cycle but inhibited MDA453 cell proliferation and reduced the proportion of MDA453 cells in S-phase of cell cycle. In both these cell lines, DHT decreased total AR messenger RNA (mRNA) but increased AR protein. In LNCaP cells, DHT down-regulated AR mRNA transcription but stabilized AR mRNA. In contrast, in MDA453 cells, DHT had no effect on AR mRNA transcription but destabilized AR mRNA. In summary, transcriptional down-regulation induced by androgens in LNCaP cells results in down-regulation of steady-state AR mRNA despite an androgen-induced increase in AR mRNA stability. However, in MDA453 cells, posttranscriptional destabilization of AR mRNA appears to be the predominant mechanism resulting in down-regulation of AR mRNA by androgen. These results demonstrate cell-specific and divergent regulation of AR mRNA turnover by androgen and identify a novel pathway of androgen-induced posttranscriptional destabilization and down-regulation of AR mRNA in human breast cancer cells. Furthermore, these data establish an important role for posttranscriptional pathways in the regulation of AR gene expression by androgen in human prostate and breast cancer cells.

scholarly journals Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor

2021 ◽  
Vol 13 (1) ◽  
pp. 17-29
Author(s):  
Emann M Rabie ◽  
Sherry X Zhang ◽  
Andreas P Kourouklis ◽  
A Nihan Kilinc ◽  
Allison K Simi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Type I ◽  
Matrix Degradation ◽  
Human Breast ◽  
Rate Of Invasion

Abstract Metastasis, the leading cause of mortality in cancer patients, depends upon the ability of cancer cells to invade into the extracellular matrix that surrounds the primary tumor and to escape into the vasculature. To investigate the features of the microenvironment that regulate invasion and escape, we generated solid microtumors of MDA-MB-231 human breast carcinoma cells within gels of type I collagen. The microtumors were formed at defined distances adjacent to an empty cavity, which served as an artificial vessel into which the constituent tumor cells could escape. To define the relative contributions of matrix degradation and cell proliferation on invasion and escape, we used pharmacological approaches to block the activity of matrix metalloproteinases (MMPs) or to arrest the cell cycle. We found that blocking MMP activity prevents both invasion and escape of the breast cancer cells. Surprisingly, blocking proliferation increases the rate of invasion but has no effect on that of escape. We found that arresting the cell cycle increases the expression of MMPs, consistent with the increased rate of invasion. To gain additional insight into the role of cell proliferation in the invasion process, we generated microtumors from cells that express the fluorescent ubiquitination-based cell cycle indicator. We found that the cells that initiate invasions are preferentially quiescent, whereas cell proliferation is associated with the extension of invasions. These data suggest that matrix degradation and cell proliferation are coupled during the invasion and escape of human breast cancer cells and highlight the critical role of matrix proteolysis in governing tumor phenotype.

scholarly journals Inhibition of MCF-7 breast cancer cell proliferation by 5alpha-dihydrotestosterone; a role for p21(Cip1/Waf1)

2004 ◽  
Vol 32 (3) ◽  
pp. 793-810 ◽  
Author(s):  
MA Greeve ◽  
RK Allan ◽  
JM Harvey ◽  
JM Bentel
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
S Phase ◽  
Cyclin D3 ◽  
P27 Kip1 ◽  
Mcf 7

Androgens inhibit the growth of breast cancer cells in vitro and in vivo by mechanisms that remain poorly defined. In this study, treatment of asynchronously growing MCF-7 breast cancer cells with the androgen, 5alpha-dihydrotestosterone (DHT), was shown to inhibit cell proliferation and induce moderate increases in the proportion of G1 phase cells. Consistent with targeting the G1-S phase transition, DHT pretreatment of MCF-7 cultures impeded the serum-induced progression of G1-arrested cells into S phase and reduced the kinase activities of cyclin-dependent kinase (Cdk)4 and Cdk2 to less than 50% of controls within 3 days. DHT treatment was associated with greater than twofold increases in the levels of the Cdk inhibitor, p27(Kip1), while p21(Cip1/Waf1) protein levels remained unchanged. During the first 24 h of DHT treatment, levels of Cdk4-associated p21(Cip1/Waf1) and p27(Kip1) were reduced coinciding with decreased levels of Cdk4-associated cyclin D3. In contrast, DHT treatment caused increased accumulation of Cdk2-associated p21(Cip1/Waf1), with no significant alterations in levels of p27(Kip1) bound to Cdk2 complexes. These findings suggest that DHT reverses the Cdk4-mediated titration of p21(Cip1/Waf1) and p27(Kip1) away from Cdk2 complexes, and that the increased association of p21(Cip1/Waf1) with Cdk2 complexes in part mediates the androgen-induced growth inhibition of breast cancer cells.

Down regulation of CSL activity inhibits cell proliferation in prostate and breast cancer cells

2011 ◽  
Vol 112 (9) ◽  
pp. 2340-2351 ◽  
Author(s):  
Thomas Yong ◽  
Amanda Sun ◽  
Michael D. Henry ◽  
Shari Meyers ◽  
J. Nathan Davis
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Down Regulation

scholarly journals Antiproliferative Effects of Cucurbitacin B in Breast Cancer Cells: Down-Regulation of the c-Myc/hTERT/Telomerase Pathway and Obstruction of the Cell Cycle

2010 ◽  
Vol 11 (12) ◽  
pp. 5323-5338 ◽  
Author(s):  
Suwit Duangmano ◽  
Sumana Dakeng ◽  
Weena Jiratchariyakul ◽  
Apichart Suksamrarn ◽  
Duncan R. Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Down Regulation ◽  
Antiproliferative Effects ◽  
Cucurbitacin B

scholarly journals Gene expression monitoring in hormone-responsive human breast cancer cells during estrogen-induced cell cycle progression

10.1038/87358 ◽  
2001 ◽  
Vol 27 (S4) ◽  
pp. 95-95
Author(s):  
Luigi Cicatiello ◽  
Angelo Facchiano ◽  
Raffaele Calogero ◽  
Michele De Bortoli ◽  
Francesco Bresciani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cell Cycle Progression ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Cycle Progression

scholarly journals Primary and Compensatory Roles for RB Family Members at Cell Cycle Gene Promoters That Are Deacetylated and Downregulated in Doxorubicin-Induced Senescence of Breast Cancer Cells

2006 ◽  
Vol 26 (7) ◽  
pp. 2501-2510 ◽  
Author(s):  
James G. Jackson ◽  
Olivia M. Pereira-Smith
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Drug Treatment ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Growth Arrest ◽  
S Phase ◽  
Cyclin B ◽  
Cell Cycle Gene ◽  
Gene Promoters

ABSTRACT When treated with DNA-damaging chemotherapy agents, many cancer cells, in vivo and in vitro, undergo a terminal growth arrest and acquire a senescence-like phenotype. We investigated the molecular basis for this in breast cancer cells following a 2-hour treatment with 1 μM doxorubicin. Treated cells arrested in G1 and G2 phases of the cell cycle, with concomitant reductions in S-phase and G2-M regulatory genes. p53 and p21 protein levels increased within hours after treatment and were maintained for 5 to 6 days but were reduced 8 days posttreatment, though the cells remained growth arrested. Levels of p130 rose after drug treatment, and it was the primary RB family member recruited to the S-phase promoters cyclin A and PCNA and G2-M promoters cyclin B and cdc2, remaining present for the entire 8-day time period. In contrast, p107 protein and promoter occupancy levels declined sharply after drug treatment. RB was recruited to only the PCNA promoter. In MCF-7 cells with p130 knockdown, p107 compensated for p130 loss at all cell cycle gene promoters examined, allowing cells to retain the growth arrest phenotype. Cells with p130 and p107 knockdown similarly arrested, while cells with knockdown of all three family members failed to downregulate cyclin A and cyclin B. These results demonstrate a mechanistic role for p130 and compensatory roles for p107 and RB in the long-term senescence-like growth arrest response of breast cancer cells to DNA damage.

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