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General Information
Name
prostate cancer (postulated), astacin-related
FlyBase ID
FBhh0000460
Disease Ontology Term
Parent Disease
OMIM
Overview

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]

Disease Summary Information
Parent Disease Summary: prostate cancer
Symptoms and phenotype

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).

Specific Disease Summary: prostate cancer (postulated), astacin-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

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).

External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Comments on ortholog(s)

Many to many (not all listed).

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many (not all listed).

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    Seminal metalloprotease-1 (Semp1) encodes a metalloprotease that is produced by male accessory glands and transferred to females during mating. It is cleavage activated during mating, first by the product of Sems and then by auto-catalysis. The product of also cleaves at least two other seminal proteins, encoded by Acp26Aa and Acp36DE, in the mated female. [Date last reviewed: 2019-03-14]
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    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.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (0 groups)
    Alleles Reported to Model Human Disease (Disease Ontology) (1 alleles)
    Models Based on Experimental Evidence ( 1 )
    Allele
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Genetic Tools, Stocks and Reagents
    Sources of Stocks
    Contact lab of origin for a reagent not available from a public stock center.
    Bloomington Stock Center Disease Page
    Selected mammalian transgenes
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila transgenes
    Allele
    Transgene
    Publicly Available Stocks
    RNAi constructs available
    Allele
    Transgene
    Publicly Available Stocks
    Selected Drosophila classical alleles
    Allele
    Allele class
    Mutagen
    Publicly Available Stocks
    amorphic allele - molecular evidence
    natural population
    References (5)