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Serotonin Regulation of Mammary Gland Involution and its Role in Breast Cancer Progression

Pai, Vaibhav Prakash
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1237565289

Abstract Details

2009, PhD, University of Cincinnati, Medicine : Molecular and Cellular Physiology.
Waves of milk production, as seen during lactation, transition into milk stasis and involution of the mammary gland, upon weaning. This transition is under homeostatic control by systemic and local regulators. Significant knowledge has been gathered regarding involvement of systemic hormones in regulating involution. However, the local factors remain largely unstudied. Previously our lab discovered serotonin as a local regulator of mammary gland milk synthesis and involution. Here we explore the influence of serotonin in regulating involution associated events, especially tight junction disruption. We show that human mammary epithelial cells have an elaborate serotonin system including serotonin reuptake transporter and multiple serotonin receptors. Through this system, serotonin employs a complex signaling mechanism to mediate fine biphasic regulation of mammary epithelial tight junctions. This is important to meet the dynamic demands associated with milk stasis and involution. Further breast cancer cells show a profound change in this serotonin system (biosynthesis and receptor expression pattern). This results in a homeostatic imbalance between the suppressive vs pro-oncogenic activites of serotonin. The breast cancer cells become resistant to involution-associated suppressive actions of serotonin and enhance the pro-oncogenic effects of serotonin (through increased serotonin synthesis). Such action of serotonin support the finding that involution is associated with increased risk of breast cancer and promotes formation of aggressive tumors.
Nelson Horseman, Ph.D. (Committee Chair)
Arthur Buckley, Ph.D. (Committee Member)
H. Leighton Grimes, Ph.D. (Committee Member)
Stuart Handwerger, M.D. (Committee Member)
Susan Waltz, Ph.D. (Committee Member)
262 p.
Biomedical Research
Serotonin; Mammary Gland; Breast Cancer

Recommended Citations

Citations

  • Pai, V. P. (2009). Serotonin Regulation of Mammary Gland Involution and its Role in Breast Cancer Progression [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1237565289

    APA Style (7th edition)

  • Pai, Vaibhav. Serotonin Regulation of Mammary Gland Involution and its Role in Breast Cancer Progression. 2009. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1237565289.

    MLA Style (8th edition)

  • Pai, Vaibhav. "Serotonin Regulation of Mammary Gland Involution and its Role in Breast Cancer Progression." Doctoral dissertation, University of Cincinnati, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1237565289

    Chicago Manual of Style (17th edition)

ucin1237565289
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© 2009, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.