Tumor associated genes in Xiphophorus - Inheritance and expression of
x-erbB. x-pdgf, x-pdgf-r, and x-erbA
Zechel C, Schleenbecker U, Peters H, Wagner E, Anders F
Genetisches Institut der Justus-Liebig-Universitšt Giessen, FRG
Certain genotypes of Xipilophorus harbour a Mendelian tumor gene complex (Tu-complex) which mediates the hereditary capacity to develop neoplasia spontaneously or following induction with initiating and promoting carcinogens. We concentrated on sex chromosome-linked tumor formation.
We cloned and partially sequenced xiphophorine genes homologous to the human c-erbB-1 (h-ergf), c-sis (h-pdgf-2), PDGF-receptor gene (h-pdgf-r) and c-erbA (h-erbA) and studied the inheritance of these genes in animals with genetic predisposition to tumor formation. So far, only a certain type of x-erbB (x-erbB*) appears to be inherited in parallel with the Tu-complex. This x-erbB*, disclosed by an X-chromosomal 4.9 kb or another 11.5 kb, and an Y-chromosomal 6.7 kb Eco R1 fragment, map to the locus of the melanoma determining Tu-complex; these genes, x-erbB*a, which are accessory show high homology to an indispensable x-erbB*i. Expression of the x-erbB*i was detected in testes, brain, gills and during embryogenesis. The x-erbB*i is expressed atto a low level in melanoma. fibrosarcoma, neuroblastoma and thyroid tumors. Fish that carrv the sex-chromosomal erbB*a express or overexpress x-erbB* in melanoma, certain fibrosarcoma and thyroid tumors. Furthermore, all tumors studied express x-pdgf-r and most of them express x-pdgf. A second type of x-erbB that was disclosed by an autosomal 5,5 kb band and probably represents the common egfr shows expression in melanoma and fibrosarcoma. Genes related to h-erbA that show differential expression during embryogenesis are expressed in normal tissue of young and adult fish but show low or no expression in tumors. So far, only the x-erbB* appears to be involved in the initial steps leading to melanoma and possibly to certain other tumors. The role of pdgf, pdgf-r, x-erbB, and x-erbA in tumor formation remains unclear.
Supported by DFG and UBA.