title: A dual prognostic role for the TGFβ receptors in human breast cancer.
abstract: The transforming growth factor-β (TGFβ) plays a dual role in breast cancer, acting as a tumor suppressor in early carcinomas while promoting tumor metastasis in more advanced breast carcinoma. As a result, the prognostic role of TGFβ and its signaling components in breast cancer remains unclear. Here we evaluated the expression levels of TGFβ signaling receptors TβRII and TβRI using human breast cancer tissue microarrays and a large publicly available gene profiling database in relation to various clinicopathological parameters. Our results indicate that breast cancer tissues express lower TβRII and TβRI protein levels compared with normal breast tissue. In contrast to TβRI expression, TβRII mRNA expression levels were also significantly downregulated in invasive breast cancer compared with normal breast tissue (4.18-fold downregulation, P=9.3×10-115). Interestingly, within the cancer cases analyzed, our results revealed a direct correlation between high TβRII and TβRI expression levels and classic poor prognostic clinicopathological parameters, including larger tumor size, advanced tumor stage, and poorly differentiated tumors. Next, we examined TGFβ receptors' expression in relation to breast cancer molecular subtypes. Importantly, our results revealed that whereas expression of TGFβ receptors in luminal A and triple-negative breast cancer showed no correlation with patient outcome, their expression in luminal B and HER2 subtypes showed significant association with favorable patient outcome. Together, these results indicate that although TGFβ receptors are downregulated in breast cancer, their expression in tumors is an indicator of aggressive breast cancer phenotype. Moreover, the relation between TGFβ pathway and patient outcome is breast cancer subtype dependent.
authors.affiliation: Division of Hematology, Cancer Research Program, Research Institute of the McGill University Health Centre, McGill University Montreal, Quebec H4A 3J1, Canada. Electronic address: Ibrahim.Hachim@mail.mcgill.ca.
authors.forename: Ibrahim Y
authors.initials: IY
authors.lastname: Hachim
authors.affiliation: Division of Medical Oncology, Department of Medicine, Cancer Research Program, Research Institute of the McGill University Health Centre, McGill University Montreal, Quebec H4A 3J1, Canada. Electronic address: mahmood.hachim@mail.mcgill.ca.
authors.forename: Mahmood Y
authors.initials: MY
authors.lastname: Hachim
authors.affiliation: Division of Hematology, Cancer Research Program, Research Institute of the McGill University Health Centre, McGill University Montreal, Quebec H4A 3J1, Canada. Electronic address: vanessa.lopez2@mail.mcgill.ca.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: López-Ozuna
authors.affiliation: Division of Hematology, Cancer Research Program, Research Institute of the McGill University Health Centre, McGill University Montreal, Quebec H4A 3J1, Canada. Electronic address: Suhad.Ali@mcgill.ca.
authors.forename: Suhad
authors.initials: S
authors.lastname: Ali
authors.affiliation: Division of Hematology, Cancer Research Program, Research Institute of the McGill University Health Centre, McGill University Montreal, Quebec H4A 3J1, Canada; Division of Medical Oncology, Department of Medicine, Cancer Research Program, Research Institute of the McGill University Health Centre, McGill University Montreal, Quebec H4A 3J1, Canada. Electronic address: JJ.Lebrun@mcgill.ca.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lebrun
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D030541:Databases, Genetic; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D010641:Phenotype; D011237:Predictive Value of Tests; D017346:Protein Serine-Threonine Kinases / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics; D013997:Time Factors; D046888:Tissue Array Analysis; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II
keywords: Breast cancer; Molecular subtypes; Patient outcomes; Prognosis; TGFβ; TGFβ receptors