biostudies-literatureUnknown5(2)Nencioni AThe efficacy of anti-HER2 therapeutics, such as lapatinib and trastuzumab, is limited by primary and acquired resistance. Cellular adaptations that allow breast cancer cell to survive prolonged HER2 inhibition include de-repression of the transcription factor FOXO3A with consequent estrogen receptor activation, and/or increased HER3 signaling. Here, we used low-density arrays, quantitative PCR, and western blotting to determine how HER2 signaling inhibition with lapatinib or PI3K inhibitors affects the expression of genes involved in breast cancer metastatic spread and overall prognosis. Retroviral transgenesis was used to express constitutively active forms of Akt in the HER2(+) breast cancer cell line SKBR3, and Grb7 in MCF7 cells. Specific gene silencing was obtained by siRNAs transfectPloS onee9024https://www.ebi.ac.uk/biostudies/studies/S-EPMC2814867biostudies-literatureGrb7 upregulation is a molecular adaptation to HER2 signaling inhibition due to removal of Akt-mediated gene repression.PMC2814867Patrone FCea MZoppoli GPassalacqua MNencioni APistoia VGaruti ASoncini DBallestrero ARaffaghello LMoran EfalseGrb7 upregulation is a molecular adaptation to HER2 signaling inhibition due to removal of Akt-mediated gene repression.The efficacy of anti-HER2 therapeutics, such as lapatinib and trastuzumab, is limited by primary and acquired resistance. Cellular adaptations that allow breast cancer cell to survive prolonged HER2 inhibition include de-repression of the transcription factor FOXO3A with consequent estrogen receptor activation, and/or increased HER3 signaling. Here, we used low-density arrays, quantitative PCR, and western blotting to determine how HER2 signaling inhibition with lapatinib or PI3K inhibitors affects the expression of genes involved in breast cancer metastatic spread and overall prognosis. Retroviral transgenesis was used to express constitutively active forms of Akt in the HER2(+) breast cancer cell line SKBR3, and Grb7 in MCF7 cells. Specific gene silencing was obtained by siRNAs transfect2010-01-01T00:00:00Z2010 Feb2026-05-29T13:09:00.717Z2025-09-01T03:06:33.82ZS-EPMC28148672012631110.1371/journal.pone.0009024