Tipping the Scales: The Role of Spy1 During Involution of the Mammary Gland
Standing
Undergraduate
Type of Proposal
Oral Presentation
Faculty
Faculty of Science
Proposal
One in eight women will be diagnosed with breast cancer in her lifetime. From puberty to menopause, factors attributed with breast cancer fluctuate with the natural development of the breasts. A period of increased breast cancer risk occurs following child-birth for five years following labour as well as increased metastatic potential with higher mortality rates. Instances of postpartum breast cancer diagnoses is in part due to the process of involution of the mammary gland: a unique biological event in which the gland reverts into non-lactating tissue. During involution, the breast undergoes intense remodelling, balancing high rates of apoptosis as well as cell regeneration comparable to that of wound healing. Disruption of these processes may lead to the occurrence of oncogenic events such as mammary epithelial hyperplasia and subsequent tumorigenesis. We hypothesize that cell cycle regulators such as the cyclin-like protein Spy1 are tightly regulated over the course of mammary gland development. Spy1 binds and activates CDKs, enabling the progression of the cell through the G1/S and G2/M checkpoints and high levels of Spy1 leads to increased susceptibility to tumorigenesis in the mammary gland. We will study the role of Spy1 during involution using both in vivo and in vitro models. In mouse models we have shown that Spy1 protein levels are elevated during involution. Using the transgenic MMTV-Spy1 murine model, a model with constitutive overexpression of Spy1 in the mammary gland, will allow study of the developmental time course of the gland during involution. Mammary gland development and involution may also be studied in vitro by replicating hormonal signals in the mouse mammary epithelial HC11 cell line, comparing overexpression of Spy1 achieved by lentiviral infection and a CRISPR-Cas9 induced HC11 Spy1-knockout lines. Understanding the role Spy1 during specific major developmental processes of the breast such as involution is central to our understanding of the events mediating tumour onset and for the development of targeted therapies.
Grand Challenges
Viable, Healthy and Safe Communities
Tipping the Scales: The Role of Spy1 During Involution of the Mammary Gland
One in eight women will be diagnosed with breast cancer in her lifetime. From puberty to menopause, factors attributed with breast cancer fluctuate with the natural development of the breasts. A period of increased breast cancer risk occurs following child-birth for five years following labour as well as increased metastatic potential with higher mortality rates. Instances of postpartum breast cancer diagnoses is in part due to the process of involution of the mammary gland: a unique biological event in which the gland reverts into non-lactating tissue. During involution, the breast undergoes intense remodelling, balancing high rates of apoptosis as well as cell regeneration comparable to that of wound healing. Disruption of these processes may lead to the occurrence of oncogenic events such as mammary epithelial hyperplasia and subsequent tumorigenesis. We hypothesize that cell cycle regulators such as the cyclin-like protein Spy1 are tightly regulated over the course of mammary gland development. Spy1 binds and activates CDKs, enabling the progression of the cell through the G1/S and G2/M checkpoints and high levels of Spy1 leads to increased susceptibility to tumorigenesis in the mammary gland. We will study the role of Spy1 during involution using both in vivo and in vitro models. In mouse models we have shown that Spy1 protein levels are elevated during involution. Using the transgenic MMTV-Spy1 murine model, a model with constitutive overexpression of Spy1 in the mammary gland, will allow study of the developmental time course of the gland during involution. Mammary gland development and involution may also be studied in vitro by replicating hormonal signals in the mouse mammary epithelial HC11 cell line, comparing overexpression of Spy1 achieved by lentiviral infection and a CRISPR-Cas9 induced HC11 Spy1-knockout lines. Understanding the role Spy1 during specific major developmental processes of the breast such as involution is central to our understanding of the events mediating tumour onset and for the development of targeted therapies.