Induction of epithelial tumors in Drosophila melanogaster heterozygous for the tumor suppressor gene wts

Abstract

The imaginal disk cells of Drosophila have a cell cycle that is very similar to that of mammalian cells. Data concerning factors inducing tumors in these cells may directly relate to the risk of these factors for inducing cancer in humans. One of the genes involved in the regulation of cell cycle control is wts (warts), the Drosophila homolog of the mammalian tumor suppressor gene LATS1. The Drosophila wts mutations are recessive lethal. However, homozygous clones that arise in heterozygous flies in the imaginal disk cells lead to epithelial tumors, spectacular outgrowths visible on the cuticle of the adult. We have treated Drosophila larvae, heterozygous for wts, with the chemical mutagen MMS (methyl methanesulfonate) or with X-rays and measured the appearance of epithelial tumors in the eclosing adult flies. This test is a variation of the well-known Drosophila somatic mutation and recombination test (SMART), where mostly recessive markers have been used leading to visible phenotypes in the eyes and wings of the fly. We show that the sensitivity of this test is far greater than the comparable test system using the recessive eye marker white.

Lapachol as an epithelial tumor inhibitor agent in Drosophila melanogaster heterozygote for tumor suppressor gene wts

“…The development and proliferation of cells of these discs in particular are not dependent on other areas of the body. This situation is very intriguing when animals are tested at a specific age; chemical compounds that can harm the DNA cause tumors to appear (Eeken et al, 2002).…”

“…To obtain wts +/+ mwh heterozygotic larvae, virgin female wts/TM3, Sb 1 (Eeken et al, 2002) were mated bred to mwh/mwh males. The larvae from this cross were treated with the chemical compound.…”

“…Tumors were only recorded when large enough to be unequivocally classified. The tumor frequency was calculated as (number of tumors / number of wts +/+ mwh flies) (Eeken et al, 2002).…”

“…Mutations in the wts genes are recessive and lethal. However, homozygotic clones that appear among heterozygotic flies in cells of imaginal discs developed epithelial tumors (previously known as warts) that are visible in the adult fly cuticles (Eeken et al, 2002). The loss or deactivation of both wts gene copies that encode a likely kinase protein depends on serine and threonine, leads to a loss of control and direction of cell proliferation in the development of the imaginal discs.…”

EFEITO ANTICARCINOGÊNICO DO GERIOOX® EM Drosophila melanogaster

“…Diversos proto-oncogenes e supressores tumorais de mamíferos encontram-se também nesta espécie, o que pode ser um auxílio na compreensão do surgimento de cânceres em humanos e animais (EEKEN et al, 2002). A similaridade entre o gene supressor de tumor warts (wts) em Drosophila com o LATS1 em humanos já foram descritas.…”