Graduate Program

Biological Sciences

Degree Name

Master of Science (MS)

Semester of Degree Completion

2007

Thesis Director

Gary Bulla

Thesis Committee Member

Ann Fritz

Thesis Committee Member

Kip McGilliard

Abstract

Using liver tumor cells and their dedifferentiated cell lines, mechanisms underlying tissue specific gene expression can be studied. We have derived cell lines, from liver tumor cells, which fail to express liver genes. These cells are termed "dedifferentiated cells". One significant observation made was that cells which fail to express liver genes also rapidly undergo programmed cell death (known as apoptosis) under the influence of the bacterial endotoxin lipopolysaccharide (LPS). Understanding the mechanism of how liver function relates to cell apoptosis is the goal of this study.

Apoptosis is known to play a critical role in development and homeostasis, yet the molecular mechanisms responsible for differences in apoptotic response in distinct cell types are poorly understood. We show that the dedifferentiated cells, unlike the parental liver tumor cells, rapidly undergo apoptosis when under the influence of LPS, indicating the hepatic function is responsible for cellular survival. We have recently found that the pathway normally implicated in cell death progression, the NF-KB pathway, is not involved in this pro-survival signaling. We asked whether other known signaling pathways played a role in LPS-mediated cell death. We examined three MAP kinase pathways. similar in their activation processes, including p38, ERK, and JNK pathways. Surprisingly, using specific pathway inhibitors, our results fail to suggest that these MAP kinase pathways are involved in LPS-mediated cell death in these dedifferentiated cell lines. These results suggest that unknown signaling pathways must be present which sense when hepatic function is compromised, resulting in an increased probability of cell death.

Download

Included in

Biology Commons

Share

COinS