This model of prostate cancer is based on the observation that the Drosophila adult male accessory gland acts as a functional homolog of the mammalian prostate. It was hypothesized that normal cell growth and migration of secondary cells in the accessory gland may be regulated by Drosophila orthologs of known regulators of human prostate cancer progression. A number of the genes in this category are highly expressed in the male accessory gland; for several these, knockdown via RNAi was shown to result in changes in the number or migration of the secondary cells. Using RNAi directed against genes highly expressed in the accessory gland and screening for similar phenotypes, additional genes were identified that contribute to the regulation of the growth and migration of accessory gland secondary cells, including Semp1. Human orthologs of the newly identified genes were shown to promote invasive activity in a human cell-line model of prostate cancer. (FBrf0226167)
Astacins are a diverse family of metalloendopeptidases with a range of functions. Dmel\Semp1 is one of multiple astacins in flies; there are also multiple astacins in human. The human gene Hsap\MEP1A has been introduced into flies.
Loss-of-function alleles or genotypes of Dmel\Semp1 are viable and fertile, without conspicuous abnormalities. For assessment of function in the accessory gland, RNAi-mediated knockdown of Semp1 was controlled by using a temperature-sensitive driver and targeting newly eclosed, newly mated males. Knockdown of Semp1 results in an increase in secondary cell migration in the accessory gland; the phenotype is variable with incomplete penetrance.
[updated Dec. 2016 by FlyBase; FBrf0222196]
Prostate cancer is the most common cancer in American men and is usually very slowly progressive; it is diagnosed in an estimated 80% of men who reach age 80 (http://www.webmd.com/prostate-cancer; 2016.12.20).
Astacins are a family of metalloendopeptidases encompassing proteins with a range of functions, including activation of growth factors, degradation of polypeptides, and processing of extracellular proteins. They are either secreted from cells or are plasma membrane-associated enzymes. [pubmed:7670368]
See 'Gene Family: Astacins' (http://www.genenames.org/cgi-bin/genefamilies/set/894).
Many to many (not all listed).
Many to many (not all listed).
Low-scoring ortholog of human astacins MEP1A and ASTL and multiple others (many Drosophila to many human). Dmel\Semp1 shares 34% identity and 49-51% similarity with human MEP1A and ASTL.
