Breast cancer in the U.S. is diagnosed in 1 in 8 women, and globally, breast cancer is the most common cancer in women.
Inherited mutations in TP53, BRCA1 and BRCA2 are among a group of genes that increase the development and progression of breast cancer. While genetics plays a role, not everyone with a family history will develop breast cancer. Additionally, external influences like environmental exposures and lifestyle factors have significant effects that can either increase or mitigate risk of breast cancer. Understanding factors driving breast cancer development are important for identifying the 1 in 8 women who are at highest risk of breast cancer and developing preventative strategies.
Emerging Research
Dr. Joseph Jerry, Ph.D. leads research as a Professor at the University of Massachusetts where he has authored over 70 manuscripts focusing on mechanisms regulating risk and resistance to breast cancer. Recent research from the research group focuses on differences in how breast cells overcome the senescence barrier allowing indefinite growth – a critical step in the development of cancers.
Cellular senescence is a normal biological process that plays an important role in maintaining normal tissues and also resists the development of cancer. Cellular senescence is an irreversible cell cycle arrest occurring in cells that have acquired mutations that can promote unregulated cell growth. This is a critical barrier that cancer cells must overcome. However, cellular senescence also limits the lifespan of cells, and thus, is an integral part of aging. Telomerase plays a key role in the maintenance of telomere length in chromosomal DNA length in stem cells but is activated in a majority of cancers allowing cells to overcome the senescence barrier.
Scientific Findings and Presentations at Three Conferences
• American Society for Biochemistry & Molecular Biology / 2024 (ASBMB) Annual Meeting
In March of 2024, Dr. Jerry’s group presented research on requirements to overcome the senescence barrier in breast epithelial cells that differ among individuals. In this work they used expression of human telomerase (TERT) in primary breast epithelial cells from normal tissue which resulted in immortalization of cells in only of 3/9 donors. The cells immortalized with TERT alone had very low levels of P16/INK4A, a cell cycle inhibitor. In contrast, expression of CDK4+TERT bypassed replicative senescence allowing stably-immortalized cell lines to be established from all 9 donors. Cells immortalized with CDK4+TERT did not silence P16/INK4A. The researchers also showed that the immortalized cells retained key markers of their identity as breast epithelial cells and inducible expression of estrogen receptor alpha (ERalpha) restored estrogen signaling and proliferation.
Details of the study titled, “Differences in barriers to immortalization in normal breast epithelial cells from donors with and without mutations in breast cancer susceptibility genes and outcomes” can be viewed in the March edition of Journal of Biological Chemistry.
• The Cancer Prevention Research Conference
The Cancer Prevention Research Conference (CPRC) is a new Joint U.S. – UK conference being held in Boston, MA on June 25-27. Researchers showcase innovative findings to help the medical community gain a better understanding of cancer and its causes, risk factors, and strategies for prevention.
Over 300 genetic variants have been shown to contribute to breast cancer risk in genome-wide association studies (GWAS). These have the potential to enhance or restrain the development of breast cancer due to exposures to environmental chemicals or inherited mutations in breast cancer susceptibility genes (e.g. TP53, BRCA1, BRCA2). Genetic diversity among patients makes it challenging to understand the nuances of the genetic mutations, the effects for cancer development, and personalized therapies for prevention and treatment of breast cancer. Therefore, cell culture models of normal breast epithelial cells are needed that represent the genetic and epigenetic diversity in women.
The highlighted study details methods and findings on “Variation in barriers to immortalization in normal breast epithelial cells and establishment of a panel of cell lines from 16 donors differing in breast cancer risk.” The results show that primary breast epithelial cells from donors with inherited mutations in BRCA1 required longer to immortalize compared to donors with no family history of breast cancer. This was accompanied by greater genetic alterations in the immortalized cells from donors with heterozygous mutations in BRCA1. The immortalized cells retain markers of both luminal and basal breast epithelial cells. The cells also exhibit p53-dependent activities indicating that this critical tumor suppressor pathway remains intact despite immortalization. These patient-derived immortalized breast epithelial cells (PD-iBECs) form hollow spheres (acinar formation) when grown in 3D matrices. Therefore, the panel of PD-iBECs provide a tool to probe the factors that can induce oncogenic transformation and how these differ among individuals.
• Buenos Aires Breast Cancer Symposium
The Buenos Aires Breast Cancer Symposium brings together a diverse group of researchers to create a multidisciplinary cancer prevention research community on September 3-6. Dr. Jerry will be among the speakers and will be presenting updated findings on the development of immortalized breast epithelial cells and differences among women in DNA damage caused by estrogen signaling.
About Dr. Joseph Jerry, Ph.D.
Dr. Jerry’s research demonstrates the importance of collaboration in pursuit of effective breast cancer therapies. He currently serves as a board member at HistoSpring and holds positions as Science Director at Pioneer Valley Life Sciences Institute, Professor of Veterinary & Animal Sciences at the University of Massachusetts Amherst, and Co-Director of Rays of Hope Center for Breast Cancer Research.
View Dr. Joseph Jerry’s authored publications to learn more about ongoing breast cancer research findings.
