Abstract
A novel spermatogenesis associated factor (SPAF) was found to be aberrantly expressed at the malignant conversion stage in a clonal epidermal model of chemical carcinogenesis. Sequence analysis revealed two ATPase modules, classifying this gene as a new member of the AAA-protein family (ATPase associated with diverse activities). Immunohistochemical staining of mouse testis sections with SPAF antibody localized expression to spermatogonia and early spermatocytes in the basal compartment of the seminiferous tubules. Northern and Western analysis of SPAF expression in testes of mice at different developmental stages confirmed its expression at early stages of spermatogenesis. In view of a mitochondrial-localization-like signal, sequence similarities to membrane-associated proteins, ATP binding properties, and intracellular expression patterns in testis, we speculate that SPAF protein may be involved in morphological and functional mitochondrial transformations during spermatogenesis. Ectopic expression of the SPAF gene in malignant epidermal cells may signify adoption of an early germ cell-like phenotype advantageous in malignant conversion.
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Acknowledgements
We thank Dr C Wenner, Dr AJ Kinniburgh, and Dr GT Bowden for critical comments. We also thank Dr P Welch for discussion and assistance in immunohistochemical analysis; Mr Joseph Brachman for immunization of rabbits; the RPCI DNA polymer facility for DNA sequencing and oligonucleotide synthesis; M Vaughan for histological assistance; and D Ogden, S Dave; and E Howley for the electron microscopy. This study was supported by NIH RO1 CA31101 and RPCI Institute Core CA16056.
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Liu, Y., Black, J., Kisiel, N. et al. SPAF, a new AAA-protein specific to early spermatogenesis and malignant conversion. Oncogene 19, 1579–1588 (2000). https://doi.org/10.1038/sj.onc.1203442
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DOI: https://doi.org/10.1038/sj.onc.1203442
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