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Leonardo
Albertini
Creator
Department of Chemistry
Bachelor of Arts
Chemistry
2019
With Honors
2019-04
Thesis advisor
Matthew
Lockett
A Paper-Based Breast Co-Culture Model to Study Direct and Indirect Effects of Endocrine Disrupting Chemicals on Estrogen Signaling
Three-dimensional (3D) cell culture platforms better recreate the complex microenvironment and cell-cell signaling gradients characteristic of in vivo tumors than monolayer cultures on plasticware. While in vitro co-culture models of stromal cells and ER(+) carcinoma cells have been developed to study tumor responses, there is a lack of detailed characterization of the expression and activity of aromatase enzyme in mammary fibroblasts in 3D environments. Aromatase converts androgens to estrogen. In this study, I quantify aromatase activity in stromal reductive mammary fibroblasts (RMFs) and estrogen receptor alpha (ERα) transactivation in a breast carcinoma cell line in 2D, 3D, and co-culture platforms. When treated with the aromatase inducers genistein and quercetin, we observed increased E2 synthesis in all culture formats containing RMFs. The 2D monocultures had much higher aromatase activity than 3D monocultures; the greatest increase in activity occurred in the co-cultures. Our results highlight the use of 3D breast cancer models as an improvement over traditional 2D cultures and a useful and efficient alternative to in vivo models.
University of North Carolina at Chapel Hill
Degree granting institution
breast cancer
carcinoma
3D cultures
endocrine disruptors
aromatase
hormone signaling
3D paper platforms
Honors Thesis
text
eng
Leonardo
Albertini
Creator
Department of Chemistry
Bachelor of Arts
Chemistry
2019
With Honors
2019-04
Thesis advisor
Matthew
Lockett
A Paper-Based Breast Co-Culture Model to Study Direct and Indirect Effects of Endocrine Disrupting Chemicals on Estrogen Signaling
Three-dimensional (3D) cell culture platforms better recreate the complex microenvironment and cell-cell signaling gradients characteristic of in vivo tumors than monolayer cultures on plasticware. While in vitro co-culture models of stromal cells and ER(+) carcinoma cells have been developed to study tumor responses, there is a lack of detailed characterization of the expression and activity of aromatase enzyme in mammary fibroblasts in 3D environments. Aromatase converts androgens to estrogen. In this study, I quantify aromatase activity in stromal reductive mammary fibroblasts (RMFs) and estrogen receptor alpha (ERα) transactivation in a breast carcinoma cell line in 2D, 3D, and co-culture platforms. When treated with the aromatase inducers genistein and quercetin, we observed increased E2 synthesis in all culture formats containing RMFs. The 2D monocultures had much higher aromatase activity than 3D monocultures; the greatest increase in activity occurred in the co-cultures. Our results highlight the use of 3D breast cancer models as an improvement over traditional 2D cultures and a useful and efficient alternative to in vivo models.
University of North Carolina at Chapel Hill
Degree granting institution
breast cancer; carcinoma; 3D cultures; endocrine disruptors; aromatase; hormone signaling; 3D paper platforms
Honors Thesis
text
eng
Aggregate Work
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yes
2020-05-13T00:00:00
unc:org:318300:faculty
unc:org:318300:staff