title: Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients.
abstract: Akt/PKB is a serine/threonine protein kinase that regulates cell cycle progression, apoptosis and growth factor mediated cell survival in association with tyrosine kinase receptors. The protein is a downstream effector of erbB-2 with implications in breast cancer progression and drug resistance in vitro. We aimed to examine the role of Akt-1 in breast cancer patients, by determining whether the expression (Akt-1) and/or activation (pAkt) were related to prognostic markers and survival. The expression of erbB-2, heregulin beta 1 and Bcl-2 was also assessed by flow cytometry or immunohistochemistry. This study comprised 93 patients, aged <50 who were treated with tamoxifen and/or goserelin. We found that pAkt was associated with lower S-phase fraction (P=0.001) and the presence of heregulin beta 1-expressing stromal cells (P=0.017). Neither Akt-1 nor pAkt was related with other factors. Tumour cells-derived heregulin beta 1 was found mainly in oestrogen receptor negative (P=0.026) and node negative (P=0.005) cases. Survival analysis revealed that pAkt positive patients were more prone to relapse with distant metastasis, independently of S-phase fraction and nodal status (multivariate analysis; P=0.004). The results suggest that activation of Akt may have prognostic relevance in breast cancer.
authors.affiliation: Department of Biomedicine and Surgery, Division of Oncology, Clinical Research Center, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden. gizpe@ibk.liu.se
authors.forename: G
authors.initials: G
authors.lastname: Pérez-Tenorio
authors.forename: O
authors.initials: O
authors.lastname: Stål
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D020890:Neuregulin-1 / Q000378:metabolism; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016196:S Phase; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004273:DNA, Neoplasm; D017273:Goserelin; D020890:Neuregulin-1; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; C087230:heregulin beta1; C494918:AKT1 protein, human