Advisory Committee Chair
Theresa Strong
Advisory Committee Members
Vithal Ghanta
Denise Shaw
Stephen Watts
Bradley Yoder
Document Type
Dissertation
Date of Award
2006
Degree Name by School
Doctor of Philosophy (PhD) College of Arts and Sciences
Abstract
Sperm protein 17 (Sp17) was initially described as a member of the rabbit sperm autoantigen family and was proposed to participate in the acrosome reaction during fertilization. Sp17 was reported to be expressed only in the testes and flagellar tails of spermatozoa, with no expression in normal somatic tissues. In contrast to early reports of its limited expression in somatic tissues, recent studies have detected Sp17 in somatic cells, most prominently in the cilia of normal epithelial cells of the larynx, trachea, fallopian tube, lung, and olfactory epithelium. It has also become apparent that Sp17 is expressed at moderate to high levels in a range of malignant murine and human cell lines and primary tumor tissues including oral squamous cell carcinoma, multiple myeloma, esthesioneuroblastoma and tumors of the ovary and nervous system. Sp17 has been primarily studied in the context of mammalian sperm function. Its biological role in somatic cells remains poorly understood despite accumulating evidence that Sp17 demonstrates more widespread expression than originally described. In this study, Sp17 was further evaluated with respect to its normal function in somatic cells and its potential role in tumorigenesis. The results demonstrate that Sp17 is expressed in basal bodies and centrosomes, suggesting that it may participate in the cell cycle based on its localization to the mitotic apparatus and midbody during mitosis in immortalized cell lines. Further, experimental over-expression of Sp17 induces changes consistent with malignant transformation in RK3E, an immortalized but nontransformed rodent epithelial iii cell line. These changes include increased cell size, enlarged nuclei, increased frequency of multinucleation, and aneuploidy as evidenced by near-tetraploid karyotypes, centrosome amplification, and multipolar mitoses. Such changes are characteristic of genetic instability which is regarded by many as an early event in tumorigenesis. These data represent the first evidence that Sp17 is a centrosome-associated protein, and that Sp17 overexpression may play an active role in tumorigenesis by promoting genetic instability.
Recommended Citation
Gaines, Jasmine P., "The Role Of Sperm Protein 17 (Sp17) In Somatic Cells And Cancer" (2006). All ETDs from UAB. 3702.
https://digitalcommons.library.uab.edu/etd-collection/3702
