A constitutively active ErbB4 mutant inhibits drug-resistant colony formation by the DU-145 and PC-3 human prostate tumor cell lines

Williams, Eric E.; Trout, Laurie J; Gallo, Richard M.; Pitfield, Sarah E.; Bryant, Ianthe; Penington, Desi J.; Riese, David J.

doi:10.1016/s0304-3835(02)00690-0

Cited by 43 publications

(76 citation statements)

References 21 publications

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“…Ψ2, PA317, and C127 cell lines are a generous gift from Daniel DiMaio (Yale University). Cell lines were cultured as described [15,16,19,20] or according to vendor recommendations with the exception that Ψ2 cells were propagated in 10% Fetal Clone III (Hyclone) instead of fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

“…Retrovirus Production -High titer amphotropic retrovirus stocks were generated as previously described [15,16,20,21].…”

Section: Methodsmentioning

confidence: 99%

“…Colony Formation Assay -Inhibition of prostate tumor cell line colony formation on plastic by ErbB4 mutants was assayed essentially as previously described [15,16,19,20]. Briefly, we infected C127, DU-145, and PC-3 cells with the recombinant amphotropic retrovirus stocks, selected for infected cells using 400 to 1100 μg/mL G418, and stained the emergent drugresistant (G418-resistant) colonies using Giemsa.…”

Section: Methodsmentioning

confidence: 99%

“…These mutants form disulfide-linked homodimers that exhibit constitutive, ligandindependent tyrosine phosphorylation [15]. Moreover, the ErbB4 Q646C mutant inhibits drugresistant colony formation in plastic dishes by the DU-145 and PC-3 human prostate cancer cell lines [16]. This suggests that ErbB4 is a bona fide prostate tumor suppressor.…”

Section: Introductionmentioning

confidence: 99%

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Phosphorylation of ErbB4 on Tyr1056 is critical for inhibition of colony formation by prostate tumor cell lines

Gallo

Bryant

Fry

et al. 2006

Biochemical and Biophysical Research Communications

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Correspondence to: David J. Riese II, Purdue Cancer Research Center, 201 S. University Street, West Lafayette, Indiana, 47907-2064, Tel (765) FAX (765) We have previously demonstrated that the constitutively-active Q646C mutant of the ErbB4 receptor tyrosine kinase inhibits colony formation by human prostate tumor cell lines. Here we use ErbB4 mutants to identify ErbB4 functions critical for inhibiting colony formation. A derivative of ErbB4 Q646 that lacks kinase activity fails to inhibit colony formation by prostate tumor cells. Likewise, an ErbB4 Q646C mutant in the context of the CT-b splicing isoform fails to inhibit colony formation. Mutation of tyrosine 1056 to phenylalanine abrogates inhibition of colony formation whereas an ErbB4 mutant that lacks all of the putative sites of tyrosine phosphorylation except for tyrosine 1056 still inhibits colony formation. Given that tyrosine 1056 is missing in the CT-b isoform, these results suggest that phosphorylation of tyrosine 1056 is critical for function. Indeed, an ErbB4 mutant that lacks kinase activity but has a glutamate phosphomimic residue substituted for tyrosine 1056 inhibits colony formation. Finally, one-dimensional phosphopeptide mapping indicates that ErbB4 Q646C is phosphorylated on tyrosine 1056. These data suggest that phosphorylation of ErbB4 tyrosine 1056 is critical for coupling ErbB4 to prostate tumor suppression.

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Section: Methodsmentioning

confidence: 99%

“…Retrovirus Production -High titer amphotropic retrovirus stocks were generated as previously described [15,16,20,21].…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Phosphorylation of ErbB4 on Tyr1056 is critical for inhibition of colony formation by prostate tumor cell lines

Gallo

Bryant

Fry

et al. 2006

Biochemical and Biophysical Research Communications

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“…ErbB4 and ErbB3 are receptors for Neuregulins (NRGs), which induce differentiation of some mammary carcinoma cell lines (Bacus et al, 1996). Agonistic ErbB4 cross-linking antibodies cause cells to differentiate (Chen et al, 1996), and constitutively active alleles of ErbB4 do not malignantly transform the growth of fibroblast or prostate cancer cell lines (Penington et al, 2002;Williams et al, 2003). Expression of ErbB4 in SUM-102 breast cancer cells enabled a differentiative response to the agonist NRG, and dominant-negative inhibition of endogenous ErbB4 in SUM44 cells reduced NRG-dependent growth inhibition (Sartor et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4

et al. 2006

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The four members of the ErbB family of receptor tyrosine kinases are involved in development and tumorigenesis of the mammary gland. Whereas the epidermal growth factor receptor, ErbB2 and ErbB3 are positively associated with various cancers, clinical studies of ErbB4 in breast cancer are contradictory. Results from tissue culture analyses and some clinical studies suggested that ErbB4 is either a tumor suppressor or is a negative regulator of ErbB2-driven tumors. Neu-Cre-ErbB4 flox/null mice in which ErbB4 was inactivated by Cre-lox-mediated recombination in the mammary gland developed MMTVNeu-driven mammary tumors with a similar latency period to mice with one or two wild-type ErbB4 alleles. Moreover, there was no difference in the histologies of tumors that developed, nor in the propensity to form lung metastases. Taken together these results suggest that ErbB4 is not a potent, highly penetrant tumor suppressor, nor is it a factor in Neu-mediated tumorigenesis in this model.

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Mutational activation of ErbB family receptor tyrosine kinases: insights into mechanisms of signal transduction and tumorigenesis

2007

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SummarySignaling by the Epidermal Growth Factor Receptor (EGFR) and related ErbB family receptor tyrosine kinases can be deregulated in human malignancies as the result of mutations in the genes that encode these receptors. The recent identification of EGFR mutations that correlate with sensitivity and resistance to EGFR tyrosine kinase inhibitors in lung and colon tumors has renewed interest in such activating mutations. Here we review current models for ligand stimulation of receptor dimerization and for activation of receptor signaling by receptor dimerization. In the context of these models, we discuss ErbB receptor mutations that affect ligand binding and those that cause constitutive receptor phosphorylation and signaling as a result of constitutive receptor dimerization. We discuss mutations in the cytoplasmic regions that affect enzymatic activity, substrate specificity and coupling to effectors and downstream signaling pathways. Finally, we discuss how emergent mechanisms of ErbB receptor mutational activation could impact the search for clinically relevant ErbB receptor mutations.

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A constitutively active ErbB4 mutant inhibits drug-resistant colony formation by the DU-145 and PC-3 human prostate tumor cell lines

Cited by 43 publications

References 21 publications

Phosphorylation of ErbB4 on Tyr1056 is critical for inhibition of colony formation by prostate tumor cell lines

Phosphorylation of ErbB4 on Tyr1056 is critical for inhibition of colony formation by prostate tumor cell lines

Formation of Neu/ErbB2-induced mammary tumors is unaffected by loss of ErbB4

Mutational activation of ErbB family receptor tyrosine kinases: insights into mechanisms of signal transduction and tumorigenesis

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