• carcinoma

This report describes an epithelial cancer model using the Drosophila genes ab, which encodes a BTB-zinc finger transcription factor, and scrib, which encodes a component of the Scribble cell polarity complex. Classical loss-of-function mutations, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for both fly genes.

Dmel\ab is a low-scoring ortholog of human ZBTB12, ZBTB37, and related genes; relatively little is known about these specific BTB-zinc finger transcription factor genes in human. Dmel\scrib is orthologous to human SCRIB and LRRC1; the mammalian SCRIB gene has been characterized as a tumor suppressor. In flies, a wild-type transgene of human Hsap\SCRIB exhibits partial heterologous rescue (functional complementation) of homozygous Dmel\scrib loss-of-function phenotypes.

Assayed in the eye-antennal disc, generation of scrib mutant clones produces adult flies with mildly reduced and necrotic eyes. Overexpression of ab in otherwise wild type eye disc clones promotes antennal disc overgrowth, and sometimes results in the formation of ectopic antennal-like structures. The combination of overexpression of ab in scrib mutant clones results in a block to pupariation and tumor overgrowth throughout an extended larval stage. Eventually, large invasive tumors develop and become fused with the larval brain lobes. Multiple genetic and physical interactions have been described for both Dmel\scrib and Dmel\ab; see below and in the corresponding gene reports.

See also the human disease model report 'cancer, epithelial, SCRIB-related' (FBhh0000587).

Experiments using Dmel\ab combination with other genes used in fly cancer models have been performed; the fly genes RhoGEF2, Src64B, and Rac1 have been assessed. Although overgrowth phenotypes are observed, they are less severe than those for ab-scrib; phenotypes are also less severe than those for the same genes combined with activated Ras85D.

[updated Nov. 2019 by FlyBase; FBrf0222196]