Differential Expression of IRS-1 and IRS-2 in UterineLeiomyosarcomas with Distinct Oncogenic Phenotypes: Lack ofCorrelation with Downstream Signaling Events

[摘要] Purpose:Insulin receptor substrates (IRSs) are essential for insulin-induced mitogenic effects on several cell types but theyalso are involved in cell transformation.We investigated whether the differential constitutive expression and potential distinctdownstream signaling events of IRS-1 and IRS-2 might be related to discrete tumourigenic phenotypes of three humanuterine leiomyosarcoma cell lines, one of which was specifically isolated for the present study.Methods and results:SK-UT-1B egressed effectively from a gellyfied Matrigel matrix and grew as did DMR cells in ananchorage-independent manner in agar and induced rapidly growing tumours in nude mice. On the contrary, SK-LMS-1cells did not emigrate from Matrigel, neither grew in agar nor were they tumourigenic. IRS-2 was highly expressed in themore malignant cell lines, whereas IRS-1 was present only in SK-LMS-1 cells. However, upon insulin stimulation both IRS-1 and IRS-2 were tyrosine phosphorylated with a similar kinetic in the respective cell lines; furthermore, after 1 min ofinsulin stimulation PI3-kinase associated with IRSs and after 2 min Shc was phosphorylated and associated with Grb2 withminor differences detectable among the various cell lines in the duration of phosphorylation and/or in their association irrespectiveof whether IRS-1 or IRS-2 were expressed.Discussion:Our findings tend to exclude that the malignancy displayed by uterine leiomyosarcomas might be directly linkedto the activation of distinct IRS-1- or IRS-2-dependent pathways.

[学科分类] 肿瘤学