The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
David C Seldin - One of the best experts on this subject based on the ideXlab platform.
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protein kinase ck2 in Mammary Gland tumorigenesis
Oncogene, 2001Co-Authors: Robert D. Cardiff, Esther Landesmanbollag, Raphaelle Romieumourez, Diane H Song, Gail E Sonenshein, David C SeldinAbstract:Protein kinase CK2 is a ubiquitous and evolutionarily conserved serine/threonine kinase that is upregulated in many human cancers and can serve as an oncogene in lymphocytes. Recently, we have demonstrated that CK2 potentiates Wnt/β-catenin signaling in Mammary epithelial cells. To determine whether CK2 overexpression contributes to Mammary tumorigenesis, we have performed comparative studies of human and rat breast cancer specimens and we have engineered transgenic mice with dysregulated expression of CK2α in the Mammary Gland. We find that CK2 is highly expressed in human breast tumor specimens and in carcinogen-induced rat Mammary tumors. Overexpression of CK2α in the Mammary Gland of transgenic mice, under control of the MMTV-LTR, causes hyperplasia and dysplasia of the female Mammary Gland. Thirty per cent of the female MMTV-CK2α transgenic mice develop Mammary adenocarcinomas at a median of 23 months of age, often associated with Wnt pathway activation, as evidenced by upregulation of β-catenin protein. NF-κB activation and upregulation of c-Myc also occur frequently. Thus, in mice, rats, and humans, dysregulated expression of CK2 is associated with and is capable of contributing to Mammary tumorigenesis. Targeted inhibition of CK2 could be useful in the treatment of breast cancer.
Gregory J Hannon - One of the best experts on this subject based on the ideXlab platform.
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an epigenetic memory of pregnancy in the mouse Mammary Gland
Cell Reports, 2015Co-Authors: Camila Dos O Santos, Egor Dolzhenko, Emily Hodges, Andrew D Smith, Gregory J HannonAbstract:Pregnancy is the major modulator of Mammary Gland activity. It induces a tremendous expansion of the Mammary epithelium and the generation of alveolar structures for milk production. Anecdotal evidence from multiparous humans indicates that the Mammary Gland may react less strongly to the first pregnancy than it does to subsequent pregnancies. Here, we verify that the mouse Mammary Gland responds more robustly to a second pregnancy, indicating that the Gland retains a long-term memory of pregnancy. A comparison of genome-wide profiles of DNA methylation in isolated Mammary cell types reveals substantial and long-lasting alterations. Since these alterations are maintained in the absence of the signal that induced them, we term them epigenetic. The majority of alterations in DNA methylation affect sites occupied by the Stat5a transcription factor and mark specific genes that are upregulated during pregnancy. We postulate that the epigenetic memory of a first pregnancy primes the activation of gene expression networks that promote Mammary Gland function in subsequent reproductive cycles. More broadly, our data indicate that physiological experience can broadly alter epigenetic states, functionally modifying the capacity of the affected cells to respond to later stimulatory events.
Esther Landesmanbollag - One of the best experts on this subject based on the ideXlab platform.
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protein kinase ck2 in Mammary Gland tumorigenesis
Oncogene, 2001Co-Authors: Robert D. Cardiff, Esther Landesmanbollag, Raphaelle Romieumourez, Diane H Song, Gail E Sonenshein, David C SeldinAbstract:Protein kinase CK2 is a ubiquitous and evolutionarily conserved serine/threonine kinase that is upregulated in many human cancers and can serve as an oncogene in lymphocytes. Recently, we have demonstrated that CK2 potentiates Wnt/β-catenin signaling in Mammary epithelial cells. To determine whether CK2 overexpression contributes to Mammary tumorigenesis, we have performed comparative studies of human and rat breast cancer specimens and we have engineered transgenic mice with dysregulated expression of CK2α in the Mammary Gland. We find that CK2 is highly expressed in human breast tumor specimens and in carcinogen-induced rat Mammary tumors. Overexpression of CK2α in the Mammary Gland of transgenic mice, under control of the MMTV-LTR, causes hyperplasia and dysplasia of the female Mammary Gland. Thirty per cent of the female MMTV-CK2α transgenic mice develop Mammary adenocarcinomas at a median of 23 months of age, often associated with Wnt pathway activation, as evidenced by upregulation of β-catenin protein. NF-κB activation and upregulation of c-Myc also occur frequently. Thus, in mice, rats, and humans, dysregulated expression of CK2 is associated with and is capable of contributing to Mammary tumorigenesis. Targeted inhibition of CK2 could be useful in the treatment of breast cancer.
Zena Werb - One of the best experts on this subject based on the ideXlab platform.
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Roles of the Innate Immune System in Mammary Gland Remodeling During Involution
Journal of Mammary Gland Biology and Neoplasia, 2007Co-Authors: Kamran Atabai, Dean Sheppard, Zena WerbAbstract:Mammary Gland involution is a period of intensive tissue remodeling. Over the course of a relatively brief period, a large proportion of the Mammary Gland epithelium undergoes programmed cell death and is removed by phagocytes. In addition, the Gland is cleared of residual milk fat globules as well as milk and adipocytes become the predominant cell type. The role of the immune system in this process has not been clearly defined. Professional phagocytes derived from the immune system can participate in the clearance of apoptotic and autophagic cells, the removal of residual milk components, and the prevention of mastitis during Mammary Gland involution. However, many of these functions can also be performed by non-professional phagocytes (e.g. Mammary epithelial cells). This review will discuss the evidence that supports a role for innate immune cells in Mammary Gland remodeling during involution.
Emily Hodges - One of the best experts on this subject based on the ideXlab platform.
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an epigenetic memory of pregnancy in the mouse Mammary Gland
Cell Reports, 2015Co-Authors: Camila Dos O Santos, Egor Dolzhenko, Emily Hodges, Andrew D Smith, Gregory J HannonAbstract:Pregnancy is the major modulator of Mammary Gland activity. It induces a tremendous expansion of the Mammary epithelium and the generation of alveolar structures for milk production. Anecdotal evidence from multiparous humans indicates that the Mammary Gland may react less strongly to the first pregnancy than it does to subsequent pregnancies. Here, we verify that the mouse Mammary Gland responds more robustly to a second pregnancy, indicating that the Gland retains a long-term memory of pregnancy. A comparison of genome-wide profiles of DNA methylation in isolated Mammary cell types reveals substantial and long-lasting alterations. Since these alterations are maintained in the absence of the signal that induced them, we term them epigenetic. The majority of alterations in DNA methylation affect sites occupied by the Stat5a transcription factor and mark specific genes that are upregulated during pregnancy. We postulate that the epigenetic memory of a first pregnancy primes the activation of gene expression networks that promote Mammary Gland function in subsequent reproductive cycles. More broadly, our data indicate that physiological experience can broadly alter epigenetic states, functionally modifying the capacity of the affected cells to respond to later stimulatory events.
