Title

Role of Spy1 in Mammary Development

Type of Proposal

Oral Presentation

Start Date

22-3-2018 9:20 AM

End Date

22-3-2018 10:40 AM

Location

Alumni Auditorium B

Faculty

Faculty of Science

Faculty Sponsor

Dr. Lisa Porter

Abstract/Description of Original Work

Breast cancer accounts for 25% of all new cancer cases in women and 13% of all cancer deaths in women. Determining the key mediators that regulate aspects of both normal and abnormal development of the breast is crucial to the development of better diagnostics and treatment options. Proper cell cycle regulation guides cellular changes during the stages of mammary development, and misregulation or mutation/deletion of key cell regulatory genes represents an important step in breast cancer initiation and progression. The cyclin-like protein Spy1 is tightly regulated during normal mammary gland development and has been implicated in several cancers, including breast cancer. Spy1 binds and activates cyclin-dependent kinases (Cdks), promoting progression through the G1/S and G2/M phase of the cell cycle. Elevated levels of Spy1 significantly increases cell proliferation and has been shown to override the DNA damage response. This study seeks to explore the question - Is Spy1 required for normal and abnormal development of the breast? My thesis work involved using the novel genome-editing tool CRISP-Cas9 to knockout Spy1 in the mouse mammary epithelial cell line HC11 and the breast cancer cell line, MDA-MB 231. These knockout cells were tested for effects on mammary cell growth and development such as proliferation, differentiation, stem cell expansion and migration. My results support that this unique family of cell cycle regulators play a critical role in the differentiation and stem cell maintenance in the mammary gland. This work sheds light on the mechanisms of normal mammary development as well as breast cancer initiation and progression and supports further exploration of this mechanism as a therapeutic direction for breast cancer.

Grand Challenges

Viable, Healthy and Safe Communities

Share

COinS
 
Mar 22nd, 9:20 AM Mar 22nd, 10:40 AM

Role of Spy1 in Mammary Development

Alumni Auditorium B

Breast cancer accounts for 25% of all new cancer cases in women and 13% of all cancer deaths in women. Determining the key mediators that regulate aspects of both normal and abnormal development of the breast is crucial to the development of better diagnostics and treatment options. Proper cell cycle regulation guides cellular changes during the stages of mammary development, and misregulation or mutation/deletion of key cell regulatory genes represents an important step in breast cancer initiation and progression. The cyclin-like protein Spy1 is tightly regulated during normal mammary gland development and has been implicated in several cancers, including breast cancer. Spy1 binds and activates cyclin-dependent kinases (Cdks), promoting progression through the G1/S and G2/M phase of the cell cycle. Elevated levels of Spy1 significantly increases cell proliferation and has been shown to override the DNA damage response. This study seeks to explore the question - Is Spy1 required for normal and abnormal development of the breast? My thesis work involved using the novel genome-editing tool CRISP-Cas9 to knockout Spy1 in the mouse mammary epithelial cell line HC11 and the breast cancer cell line, MDA-MB 231. These knockout cells were tested for effects on mammary cell growth and development such as proliferation, differentiation, stem cell expansion and migration. My results support that this unique family of cell cycle regulators play a critical role in the differentiation and stem cell maintenance in the mammary gland. This work sheds light on the mechanisms of normal mammary development as well as breast cancer initiation and progression and supports further exploration of this mechanism as a therapeutic direction for breast cancer.