PgmNr Z6035: Investigating role of breast tumor kinase/protein tyrosine kinase 6 (Brk/PTK6) during zebrafish development using TALEN-generated knockout alleles.

Authors:
S. Foster 1 ; S. Glover 1 ; A. Challa 1 ; K. Chatti 2


Institutes
1) University of Alabama at Birmingham, AL; 2) University of Hyderabad Campus, Hyderabad, India.


Abstract:

Breast tumor kinase/protein tyrosine kinase 6 (Brk/PTK6) was initially discovered in a screen of tyrosine kinases overexpressed in metastatic breast cancer tissue. It is currently known to be expressed in several cancer types, and cell culture studies indicate a pro-oncogenic role for PTK6. PTK6-null mice are viable, but show hyperproliferation of colonic villi and hyperactivation of AKT. Contrasting evidence supporting a pro-apoptotic role of PTK6 has also been reported. In cultured non-cancer cells, PTK6 appears to sensitize the cells to inducers of apoptosis. The contrasting functions of PTK6 are likely to be a result of cell-type specific genetic interactions, biochemical regulation and environmental effects during oncogenesis. In order to gain a comprehensive understanding of the developmental role of PTK6 genes and to potentially explain their contrasting effects on cell growth and differentiation in vertebrates, we generated several indel alleles of the two zebrafish genes ptk6a and 6b using TALENs. Our current findings suggest that homozygous mutant animals are viable presumably because these two genes complement each other, or because of maternal expression of the genes that can rescue the zygotic loss-of-function. Further characterization is underway to generate and analyze double mutants as well as maternal-zygotic mutant animals for each of these genes to identify any developmental roles.



ZFIN Genetics Index
1. ZDB-GENE-081105-117
2. ZDB-GENE-060929-1150