Effects of Estrogen Deprivations on Hormone Responsive Breast Cancer Cell Lines PDF Download
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Author: John J. Pink
Publisher:
ISBN:
Category :
Languages : en
Pages : 642
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Book Description
Author: John J. Pink
Publisher:
ISBN:
Category :
Languages : en
Pages : 642
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Book Description
Author: Ethel M. Cormier
Publisher:
ISBN:
Category :
Languages : en
Pages : 488
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Book Description
Author: Catherine Sue Murphy
Publisher:
ISBN:
Category :
Languages : en
Pages : 358
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Book Description
Author: W. R. Miller
Publisher: Landes Bioscience
ISBN:
Category : Medical
Languages : en
Pages : 234
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Book Description
Author: Fritz F. Parl
Publisher: IOS Press
ISBN: 9780967335544
Category : Breast
Languages : en
Pages : 280
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Book Description
Estrogens have been implicated to play a role in the development of breast cancer. The purpose of this book is to provide a comprehensive analysis of experimental, clinical and epidemiological evidence in support of the carcinogenicity of estrogens.
Author: Shyam Narayan Sundar
Publisher:
ISBN:
Category :
Languages : en
Pages : 438
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Book Description
Author: Virgil Craig Jordan
Publisher: Univ of Wisconsin Press
ISBN: 9780299104801
Category : Breast
Languages : en
Pages : 564
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Book Description
This book marks one of the achievements of the "Estrogen and Antiestrogen Action: Basic and Clinical Aspects" Wisconsin Clinical Cancer Center conference in June 1984. It is not intended to be a recount of the meeting proceedings but is, rather, a historical review of the development of this field of endeavor during the past 30 years. The chapters have been written by many of the leading experts in the field who were asked to recount the development of a particular area or laboratory idea in which they had been personally involved. The book is intended to provide both scientists and clinicians with a single-volume overview of both the basic principles of hormonal control of breast cancer and the recent clinical results from cooperative groups around the world.
Author: Fatou Jallow
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Approximately 75% of breast cancers are estrogen receptor alpha positive (ER[alpha]+). Accordingly, antiestrogens which target ER activity are standard for patients with ER[alpha]+ breast cancer. However, despite significant benefits from antiestrogen treatment, resistance is common and significantly influences the overall mortality in ER[alpha]+ breast cancer patients. The mechanisms that lead to resistance are not well understood, but one postulated mechanism is that ER[alpha] is activated in the absence of estrogenic ligand. Prolactin (PRL) is a cytokine that is elevated in the local breast cancer environment and has been implicated in resistance to therapy. PRL canonically signals to activate signal transducers and activators of transcription 5a/b (STAT5A/B). STAT5A mediates most of the physiologic actions of PRL in the mammary gland and is considered a positive prognostic factor in breast cancer, while STAT5B induces migration and invasion of breast cancer cell lines. PRL and estrogen (E2) crosstalk at multiple levels in both normal mammary development and in mammary tumors. PRL and E2 have been shown to regulate each other's receptor and both contribute to the maturation of the mammary gland. Furthermore, the ability of E2 to crosstalk with STAT5 has been presented in several studies, however, the data failed to distinguish between STAT5A and STAT5B. Additionally, the mechanisms underlying these processes between the different hormones/proteins are not well understood. To investigate the ability of PRL to functionally activate ER[alpha] in the absence of ligand in vivo, we utilized genetically modified mouse models. A "knocked-in" ER[alpha] with a mutation in the ligand-binding pocket (G525L) prevents the binding of endogenous 17[beta]-estradiol (E2), but retains the ability to be activated by phosphorylation and responds to the synthetic ER[alpha] agonist, propyl pyrazole triol (PPT). Our findings revealed that PRL was sufficient to activate ER[alpha] in the absence of estrogenic ligand and cooperated with TGF[alpha] to increase ductal proliferation, which was significantly decreased by ICI182,780 (ICI). In contrast to the effects on ductal proliferation, ICI reduced tumor latency in PRL/TGF[alpha] females and significantly increased STAT5B transcript and protein. With these data, I hypothesized that estrogen signals alter STAT5 isoform expression in mammary epithelia, which modifies cellular behavior. To test this hypothesis, we utilized a "normal" mouse mammary epithelial cell line (HC11) and two mouse mammary tumor cell lines (TC2 and TC11) generated from an NRL-PRL ER[alpha]+ adenocarcinoma. These data demonstrated that in "normal" and tumor cell lines, E2 increased STAT5A, which was associated with transcripts indicating a more differentiated phenotype and ICI increased STAT5B, which was associated with a more aggressive phenotype. However, E2 also significantly increased proliferation, invasion and stem cell-like activity in the tumor cells, while ICI had no effect. To evaluate the role of STAT5B in these responses, we reduced STAT5B expression using shRNA. shSTAT5B blocked ICI-induced transcripts associated with metastasis and the epithelial-to-mesenchymal transition in both cell types. shSTAT5B also blocked E2-induced invasion of tumor epithelium, without altering E2-induced transcripts. Together, these studies indicate that STAT5B mediates a subset of pro-tumorigenic responses to both E2 and ICI, highlighting the need to better understand regulation of its expression and suggesting exploration as a possible therapeutic target in breast cancer. The role of E2 in breast cancer is well established, however, these data reveal the importance of the crosstalk between E2 and other hormones in the tumor cells. To further evaluate the role of E2 signaling in treatment resistance, we utilized a mutant mouse model with a collagen-I dense environment (mCol1a1). While the contributions of the extracellular matrix to progression of cancer are increasingly appreciated, the effects of properties of the extracellular matrix on hormone signaling and therapeutic responsiveness of ER[alpha]+ breast cancer have not been fully examined. To study hormone actions in ER[alpha]+ breast tumors and the bidirectional crosstalk with the tumor microenvironment, we employed the TC11 cell line. These cells were orthotopically transplanted into the caudal mammary fat pads of 8-week-old wild-type (WT) or mCol1a1 syngeneic FVB/N female mice. After tumors were established, recipients received 17[beta]-estradiol (E2), or tamoxifen treatment and then allowed to grow to end-stage. As expected, E2 increased tumor growth and proliferation in both genotypes. Interestingly, tamoxifen switched to an agonist in the mCol1a1 female recipients, increasing both tumor growth and proliferation. The collagen-I dense environment was sufficient to increase c-Jun activity, which was further enhanced with E2 and tamoxifen treatment. Moreover, the collagen-I dense environment increased frequency of lung metastases but estrogen activity had no effects. However, E2 significantly increased the size of the lung metastases in WT female recipients and was augmented in the mCol1a1 female recipients. These data support the significance of the collagen-I dense environment and its effects on E2 responsiveness and effective antagonism by tamoxifen
Author: Shun-Yuan Jiang
Publisher:
ISBN:
Category :
Languages : en
Pages : 346
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Book Description
Author: Jose Russo
Publisher: World Scientific
ISBN: 9813271213
Category : Medical
Languages : en
Pages : 688
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Book Description
This narrative of a cancer researcher spans a period in which biomedicine research has been so revolutionary. The educational background and socioeconomic circumstances of the author make the story unique, shedding light on many important intellectual achievements. The author also provides an insightful view on how decisions at the upper echelon of scientific institutions affect cancer researchers. The vivid account of scientific discovery and intellectual evolution provides a fine example for the next generation of cancer researchers.
