No description available.

Thesis (DR. P.H.)--University of Michigan.

Thesis (DR. P.H.)--University of Michigan.

Thesis (M. Phil.)--University of Hong Kong, 1996. / Includes bibliographical references (leaf 193-235).

Thesis (M. Med. Sc.)--University of Hong Kong, 2005.

Thesis (MTech (Biomedical Technology))--Cape Technikon, 2011. / Cancer of the prostate gland is now recognised as one of the principal medical problems in males. In the USA, cancer of the prostate is the second most commonly diagnosed cancer after skin cancer and the second most common cause of death from cancer after lung cancer. In South Africa, prostate cancer is the second most common cancer, with an estimated annual incidence of 19.1 per LOO000 men (Sitas, 1994). However, this incidence is probably under-estimated, due to incomplete records. Comparison of the incidence of prostate cancer in the different racial groups shows that it is the second most common malignancy in the White, Black (African) and Mixed (Coloured) race groups, and the fourth most common malignancy in Asian (Indian) men in South Africa. Metastatic prostate cancer is refractory to hormone therapy and remains incurable. Hence, novel therapeutic approaches are needed. These anticancer drugs can be tested in tumour cell lines, and cell culture methods also permit testing of optimum conditions.

ABF-1 is a human class ll basic helix-loop-helix transcription factor that is expressed predominately in EBV immortalized and activated B lymphocytes. A human cell line was stably transfected with a tetracycline regulated ABF-1 expression vector. The cell line revealed tight regulation of ABF-1 expression following stable incorporation of the vector into the genomic DNA. Upon induction of ABF-1 expression, the cell line exhibited a dramatic growth rate decrease. In order to monitor genes regulated by ABF-1, cells were collected both before and after induced ABF-1 expression and subjected to a microarray analysis. Early interpretations of the microarray data support the findings that ABF-1 may be regulating gene expression in a manner that facilitates withdrawal from the cell cycle.

The basic helix-loop-helix protein, activated B-cell factor-l (ABF-l), is a transcription factor involved in cellular proliferation and differentiation. ABF-1 shows patterns of expression that are stimulated in activated B cells, which may suggest ABF-1 is involved in the regulation of B-cell differentiation. To investigate the functional role of ABF-1, we have generated a human plasmacytoma cell line with inducible expression of ABF-1. We were able to induce expression of ABF-1 by using the tetracycline repressor system (teton/off). With addition of tetracycline we were able to stimulate the expression of the full-length ABF-1 in the cells. We also got induction of the truncated form of ABF-1, lacking the protein dimerization domain (HLH), with the addition of tetracycline. We then compared these two cell lines to uninduced cells. We confirmed that ABF-1 expression was induced by western blot analysis. We conclude that we have developed a human plasmacytoma cell line with inducible expression of ABF-1 and can use this cell line for further studies.

Activated B-cell Factor-I (ABF-1) is a class II basic helix-loop-helix protein expressed in activated B-cells, EBV -immortalized lymphoblastoid cell lines and embryonic skeletal muscle in mice. ABF -1 dimerizes with another bHLH protein E4 7 to form a transcriptional repressor ofE2A, which is a gene essential to the proper development of B- and T -cells. In an effort to study genes in B-cells regulated by ABF- 1, I have attempted to construct a Burkitt Lymphoma cell line allowing tetracycline regulated expression of ABF-1. The tetracycline repressor gene was first added to these cells, creating a parental line oftet repression. Next, both a full-length and a truncated version of ABF -1 were added to the cell line. The truncated version of the protein is expressed in the presence of tetracycline, but completely repressed in its absence, demonstrating a tightly-regulated system of inducible expression. The full-length version of ABF-1 has yet to be expressed in this cell line; however, it has been expressed in a HeLa cell line, demonstrating that the construct has been properly made.

No description available.