The tyrphostin B42 inhibits cell proliferation and HER-2 autophosphorylation in cervical carcinoma cell lines.
The HER family receptors have an important role controlling cell growth and differentiation. Although the activity of the HER-2 receptor is strictly controlled in normal cells, its overexpression plays a pivotal role in transformation and tumorigenesis. Constitutive phosphorylation of HER-2 protein has been implicated in conferring uncontrolled growth to mammary cancer cells, and to a lesser extent, with adenocarcinoma of uterus, cervix, fallopian tube, and endometrium. This study addresses the role of HER-2 in cervical carcinoma. Firstly, we demonstrate the presence of HER-2 protein expression by flow cytometry in two new cervical carcinoma cell lines CALO and INBL. Secondly, we use the specific tyrosine kinase inhibitors, Tyrphostins to examine HER-2 regulation by the crystal violet assay. Thirdly, we use western blot analysis to assess the state of HER-2 phosphorylation. The most efficient agent, Tyrphostin B42, known as an inhibitor of epithelial growth factor receptor, arrested cervical carcinoma cell lines growth in vitro at micromolar concentrations within 72 h of application. Tyrphostin B42 inhibited the HER2 signal-regulated kinase pathway, as observed by the reduction in the phosphorylated forms of HER2. The loss of phosphorylated forms of HER2 at early time points after Tyrphostin B42 application was associated with suppression of cell growth. Thus, the inhibition of the proliferation of our cervical carcinoma cell lines by Tyrphostin B42 is associated with inhibition of HER2 protein kinase signal.
Soto-Cruz
Isabel
I
Laboratory of Oncology, Research Unit in Cell Differentiation and Cancer, Facultad de Estudios Superiores Zaragoza, Iztapalapa, México.
Rangel-Corona
Rosalva
R
Valle-Mendiola
Arturo
A
Moreno-Morales
Xóchitl
X
Santiago-Pérez
Rocío
R
Weiss-Steider
Benny
B
Cáceres-Cortés
Julio R
JR
D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*
D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D014443:Tyrosine; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide