TY - JOUR
T1 - Differential expression of IRS-1 and IRS-2 in uterine leiomyosarcomas with distinct oncogenic phenotypes
T2 - Lack of correlation with downstream signaling events
AU - Colombatti, Alfonso
AU - Russo, Pietro
AU - Cervi, Marta
AU - Bogetto, Laura
AU - Wassermann, Bruna
AU - Mainiero, Fabrizio
AU - Spessotto, Paola
PY - 2002/9
Y1 - 2002/9
N2 - 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.
AB - 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.
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U2 - 10.1080/1357714021000065387
DO - 10.1080/1357714021000065387
M3 - Article
C2 - 18521338
AN - SCOPUS:0036765219
VL - 6
SP - 89
EP - 96
JO - Sarcoma
JF - Sarcoma
SN - 1357-714X
IS - 3
ER -