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 sel. Human orthologs of the newly identified genes were shown to promote invasive activity in a human cell-line model of prostate cancer. (FBrf0226167)
Dmel\sel is orthologous to two human genes, CNPY2 and CNPY1. These genes encode transmembrane proteins localized to the endoplasmic reticulum; they may play roles in the regulation of signal transduction pathways. A UAS construct of a tagged human Hsap\CNPY2 gene has been introduced into flies, but has not been characterized in the context of this disease model.
Loss-of-function mutations of Dmel\sel are female sterile, due to a maternal effect that results in embryonic lethality. For assessment of function in the accessory gland, RNAi-mediated knockdown of sel was controlled by using a temperature-sensitive driver and targeting newly eclosed, newly mated males. Knockdown of sel results in a decrease in the number of secondary cells compared to controls; the phenotype is variable with incomplete penetrance. Physical interactions of Dmel\sel have been characterized; see below and in the gene report for sel.
[updated Feb. 2019 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).
The Dmel\sel gene encodes a transmembrane protein localized to the endoplasmic reticulum; it may play a role in the regulation of signal transduction pathways, including during very early establishment of dorsal-ventral polarity (FBrf0212238).
Many to one: 2 human to 1 Drosophila.
Many to one: 2 human to 1 Drosophila.
High-scoring ortholog of human CNPY2, moderate-scoring ortholog of human CNPY1 (1 Drosophila to 2 human). Dmel\sel shares 30% identity and 56% similarity with human CNPY2.
