Graduation Year

2017

Document Type

Honors Thesis

Degree Name

Bachelor of Arts

Department

Natural Sciences

Program or Major

Biology

Faculty Advisor

Jessica McCready

Abstract

Introduction: The cellular retinoic acid binding protein 1 (Crabp1) promotes tumor growth and is expressed in adipocyte stromal cells (ASCs-L) present during lactation. One known function of Crabp1 is the binding and retention of retinoic acid (RA) in the cytoplasm. This can prevent RA regulated transcription of other genes. Research has shown that Crabp1 is also responsible for the inability of ASC-Ls to retain lipid. This study hoped to connect these two functions of Crabp1 and hypothesized that Crabp1 limits lipid accumulation through Fatty acid synthase (FAS) transcriptional regulation. FAS is an example of a gene that is regulated by RA.

Methods: Luciferase assays, RT-qPCR, and Oil Red O assays were performed to study FAS promoter activity, mRNA levels, and lipid accumulation, respectively. ASCs at different stages of mammary gland development were studied to determine the relationship between Crabp1, FAS, and lipid accumulation upon RA treatment.

Results: Our results suggest that RA treatment leads to a decrease in FAS promoter activity as well as FAS and Crabp1 mRNA levels in ASC-Nulliparous. Furthermore, higher Crabp1 mRNA levels in ASC-Ls did not correlate with a decrease in FAS mRNA. ASC-Ls also showed low lipid accumulation in the presence of adipocyte differentiation media, suggesting that Crabp1 regulates lipid accumulation, but not through the regulation of FAS.

Conclusion: The mechanisms of Crabp1 in lipid regulation of ASCs remains to be determined. Our data show that Crabp1 does not regulate FAS though RA retention in ASC-Ls. However, our results are consistent with the literature in that ASC-Ls have high levels of Crabp1, but low lipid accumulation. Through understanding how Crabp1 is acting on the adipocytes in the mammary gland it can be better understood what its tumor promoting function is in PABCs.

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