PMID- 18521338 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20110714 LR - 20211020 IS - 1357-714X (Print) IS - 1369-1643 (Electronic) IS - 1357-714X (Linking) VI - 6 IP - 3 DP - 2002 TI - Differential Expression of IRS-1 and IRS-2 in Uterine Leiomyosarcomas with Distinct Oncogenic Phenotypes: Lack of Correlation with Downstream Signaling Events. PG - 89-96 LID - 10.1080/1357714021000065387 [doi] 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. FAU - Colombatti, Alfonso AU - Colombatti A AD - Divisione di Oncologia Sperimentale 2 Centro di Riferimento Oncologico-IRCCS Aviano 33081 Italy. FAU - Russo, Pietro AU - Russo P FAU - Cervi, Marta AU - Cervi M FAU - Bogetto, Laura AU - Bogetto L FAU - Wassermann, Bruna AU - Wassermann B FAU - Mainiero, Fabrizio AU - Mainiero F FAU - Spessotto, Paola AU - Spessotto P LA - eng PT - Journal Article PL - Egypt TA - Sarcoma JT - Sarcoma JID - 9709257 PMC - PMC2395487 EDAT- 2008/06/04 09:00 MHDA- 2008/06/04 09:01 PMCR- 2002/09/01 CRDT- 2008/06/04 09:00 PHST- 2008/06/04 09:00 [pubmed] PHST- 2008/06/04 09:01 [medline] PHST- 2008/06/04 09:00 [entrez] PHST- 2002/09/01 00:00 [pmc-release] AID - S1357714X02000269 [pii] AID - 10.1080/1357714021000065387 [doi] PST - ppublish SO - Sarcoma. 2002;6(3):89-96. doi: 10.1080/1357714021000065387.