Assessment of epidermal growth factor receptor (EGFR, ErbB1) and HER2 (ErbB2) protein expression levels and response to lapatinib (Tykerb, GW572016) in an expanded panel of human normal and tumour cell lines.

OBJECTIVE: Lapatinib (Tykerb, GW572016), a potent inhibitor of the catalytic activities of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (ErbB2), inhibits population growth of selected EGFR and HER2 overexpressing cell lines. Previous studies with a small number of cell lines suggest a correlation between overexpression of EGFR and/or HER2 and sensitivity to growth inhibition by lapatinib; however, the precise determinants of lapatinib selectivity for tumour and/or other cells remain unclear. MATERIALS AND METHODS: To clarify the determinants of its selectivity in cultured cells, lapatinib-induced cell population growth inhibition and relative EGFR and HER2 protein expression were quantified in 61 different human tumour cell lines from 12 tumour types, two oncogene transformed human cell lines and two normal human cell cultures. Using statistical tools to analyse the data, a model describing the relationship between lapatinib IC(50) (the response variable) and EGFR and HER2 expression and tissue type (explanatory variables) was derived. CONCLUSION: The results suggest that simultaneous consideration of EGFR and HER2 expression, as well as tissue type yields the best determinant of lapatinib selectivity in cultured cells.

Unexpected ratio of allozyme expression in diploid and triploid individuals of the clonal hybrid fish Phoxinus eos-neogaeus.

Phoxinus eos-neogaeus, a North American freshwater fish, was formed by hybridization between P. neogaeus and P. eos. Individuals of P. eos-neogaeus express one allozyme of P. eos and one allozyme of P. neogaeus for enzymes for which the parental allozymes are distinctive. We performed densitometry on phosphoglucomutase (PGM) and one glucose-6-phosphate isomerase locus (GPI-A) separated by cellulose acetate electrophoresis to determine if the parental species' allozymes are expressed in proportion to the number of genomes present in diploid and triploid individuals, and if these enzymes are regulated separately in different tissues. In diploids, activity of the P. eos allozyme was greater than the P. neogaeus allozyme in eye, liver, and muscle but not in heart (one sample t-test, P = 0.05) for PGM. The activity of the P. eos GPI-A allozyme was significantly greater than the P. neogaeus allozyme in heart, eye and muscle but not in liver (one sample t-test, P = 0.05). The expected ratio of eos:neogaeus expression in triploid P. eos-neogaeus x eos individuals is 2:1. For PGM, the observed ratio of eos:neogaeus expression was not significantly different from 2:1 in all four tissues. The P. eos allozyme for GPI was expressed less than expected in all four tissues (one-sample t-test, P = 0.05). Thus, greater than expected expression of the P. eos allozyme was not observed in triploid individuals as it was in the diploids. These data show that PGM and GPI are regulated separately, and that regulation differs by tissue, and in fish of distinct ploidy levels. J. Exp. Zool. 284:663-674, 1999.