Differential expression of IRS-1 and IRS-2 in uterine leiomyosarcomas with distinct oncogenic phenotypes: Lack of correlation with downstream signaling events

Alfonso Colombatti, Pietro Russo, Marta Cervi, Laura Bogetto, Bruna Wassermann, Fabrizio Mainiero, Paola Spessotto

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)89-96
Number of pages8
JournalSarcoma
Volume6
Issue number3
DOIs
Publication statusPublished - Sep 2002

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Insulin Receptor Substrate Proteins
Leiomyosarcoma
Phenotype
Cell Line
Insulin
Agar
Insulin Receptor
Phosphatidylinositol 3-Kinases
Nude Mice
Neoplasms
Phosphorylation

ASJC Scopus subject areas

  • Oncology

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Differential expression of IRS-1 and IRS-2 in uterine leiomyosarcomas with distinct oncogenic phenotypes : Lack of correlation with downstream signaling events. / Colombatti, Alfonso; Russo, Pietro; Cervi, Marta; Bogetto, Laura; Wassermann, Bruna; Mainiero, Fabrizio; Spessotto, Paola.

In: Sarcoma, Vol. 6, No. 3, 09.2002, p. 89-96.

Research output: Contribution to journalArticle

Colombatti, Alfonso ; Russo, Pietro ; Cervi, Marta ; Bogetto, Laura ; Wassermann, Bruna ; Mainiero, Fabrizio ; Spessotto, Paola. / Differential expression of IRS-1 and IRS-2 in uterine leiomyosarcomas with distinct oncogenic phenotypes : Lack of correlation with downstream signaling events. In: Sarcoma. 2002 ; Vol. 6, No. 3. pp. 89-96.
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