Clinical Value of RPS6KB1 and RPS6KB2 Gene Amplification in Postmenopausal Breast Cancer
2008 (English)Article in journal (Refereed) Submitted
The mammalian target of rapamycin (mTOR) and its substrates the ribosomal S6 kinases (S6K)1 and 2 integrate nutrient and hormonal/growth factor mediated signals and are implicated indiabetes, obesity and cancer. The genes encoding S6K1 (RPS6KB1) and S6K2 (RPS6KB2) aresituated close to well known amplicons but information regarding its expression and clinicalvalue is scarce. In this study we quantified RPS6KB1/2 gene copy number, establishedassociations with other clinical factors and explored their clinical value in breast cancer. RPS6KB1/2 copy number was determined by fast real-time PCR in 207 breast tumors.RPS6KB1 was amplified (≥ 4 copies) in 10.7% (22/206) and RPS6KB2 in 4.3% (9/207) of thetumors. Amplification of RPS6KB1 was associated with HER2 gene amplification (P=0.025)and protein expression (P=0.014) while RPS6KB2 correlated with ER+ status (P=0.046) and CCND1 amplification (P<0.00001). In a multivariate analysis, both genes were independentprognostic factors indicating higher risk to develop recurrences. In terms of loco regionalcontrol, amplification of the RPS6KB1 gene predicted less response to radiotherapy (P=0.035) while RPS6KB2 gene copy gain (≥ 3 copies) indicated increased benefit from tamoxifen (P=0.03) among ER+ patients. S6K1/2 gene amplification could be used as an indicator oftherapy response among postmenopausal breast cancer patients.
Place, publisher, year, edition, pages
PI3K, AKT, mTOR, CCND1, HER2, ER, Tamoxifen
National CategoryCancer and Oncology
IdentifiersURN: urn:nbn:se:liu:diva-15042OAI: oai:DiVA.org:liu-15042DiVA: diva2:37728