Differential Expression of IRS-1 and IRS-2 in Uterine Leiomyosarcomas with Distinct Oncogenic Phenotypes: Lack of Correlation with Downstream Signaling Events.

Autor: Colombatti A; Divisione di Oncologia Sperimentale 2 Centro di Riferimento Oncologico-IRCCS Aviano 33081 Italy., Russo P, Cervi M, Bogetto L, Wassermann B, Mainiero F, Spessotto P
Jazyk: angličtina
Zdroj: Sarcoma [Sarcoma] 2002; Vol. 6 (3), pp. 89-96.
DOI: 10.1080/1357714021000065387
Abstrakt: Purpose: Insulin receptor substrates (IRSs) are essential for insulin-induced mitogenic effects on several cell types but they also are involved in cell transformation.We investigated whether the differential constitutive expression and potential distinct downstream signaling events of IRS-1 and IRS-2 might be related to discrete tumourigenic phenotypes of three human uterine 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 an anchorage-independent manner in agar and induced rapidly growing tumours in nude mice. On the contrary, SK-LMS-1 cells did not emigrate from Matrigel, neither grew in agar nor were they tumourigenic. IRS-2 was highly expressed in the more 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 of insulin stimulation PI3-kinase associated with IRSs and after 2 min Shc was phosphorylated and associated with Grb2 with minor differences detectable among the various cell lines in the duration of phosphorylation and/or in their association irrespective of whether IRS-1 or IRS-2 were expressed.
Discussion: Our findings tend to exclude that the malignancy displayed by uterine leiomyosarcomas might be directly linked to the activation of distinct IRS-1- or IRS-2-dependent pathways.
Databáze: MEDLINE
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