Masters Theses

Date of Award

8-1991

Degree Type

Thesis

Degree Name

Master of Science

Major

Biochemistry and Cellular and Molecular Biology

Major Professor

John W. Koontz

Committee Members

J. Churchich, W.D. Wicks

Abstract

The albumin gene is expressed in a liver specific and developmentally regulated manner. Its constitutive expression requires the liver specific transcription factor HNF-1 (hepatocyte nuclear factor-1). HNF-1, like albumin, is only present in cells that display the adult liver phenotype. The presence of HNF-1 or vHNF-1, a variant form found in fetal liver cells, has become an additional criterion used to characterize liver cells. The KRC7 rat hepatoma cells were examined for the presence of HNF-1/vHNF-1 and for the presence of albumin mRNA. It was demonstrated that the KRC7 cells produce HNF-1 and transcribe the albumin gene. Two well characterized rat hepatoma cell lines were used for comparison. The C2 cell line was representative of a fetal or dedifferentiated line and the Fao cell line was representative of the adult liver phenotype. It has been shown that glucocorticoids are able to increase transcription of several liver specific genes, and the effect of dexamethasone on albumin transcription was measured. Glucocorticoids are able to increase albumin mRNA levels in all three of the hepatoma cell lines. This increase has been characterized in the C2 and KRC7 cell lines. Time course and concentration dependence experiments were performed. The half maximal response occurs at the same concentration in both cell lines. The induction is resistant to the protein synthesis inhibitor cycloheximide. Also, the stability of the transcript was compared in the two cell lines and found to be the same. The form of HNF-1 produced by the cells is not affected by dexamethasone. Therefore, the C2 cells are capable of transcribing the albumin gene without the adult form of HNF-1.

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