Depletion of the Transcriptional Coactivator Amplified in Breast Cancer 1 (AIB1) Uncovers Functionally Distinct Subpopulations in Triple-Negative Breast Cancer.

Depletion of the Transcriptional Coactivator Amplified in Breast Cancer 1 (AIB1) Uncovers Functionally Distinct Subpopulations in Triple-Negative Breast Cancer. Neoplasia. 2019 Aug 19;21(10):963-973 Authors: Saenz FR, Ory V, Schmidt MO, Kallakury BV, Mueller SC, Furth PA, Wellstein A, Riegel AT Abstract The transcriptional coactivator Amplified in Breast Cancer 1 (AIB1) plays a major role in the progression of hormone and HER2-dependent breast cancers but its role in triple negative breast cancer (TNBC) is undefined. Here, we report that established TNBC cell lines, as well as cells from a TNBC patient-derived xenograft (PDX) that survive chemotherapy treatment in vitro express lower levels of AIB1 protein. The surviving cell population has an impaired tube-formation phenotype when cultured onto basement membrane, a property shared with TNBC cells that survive shRNA-mediated depletion of AIB1 (AIB1LOW cells). DNA analysis by exome sequencing revealed that AIB1LOW cells represent a distinct subpopulation. Consistent with their in vitro phenotype AIB1LOW cells implanted orthotopically generated slower growing tumors with less capacity for pulmonary metastases. Gene expression analysis of cultured cells and tumors revealed that AIB1LOW cells display a distinct expression signature of genes in pro-inflammatory pathways, cell adhesion, proteolysis and tissue remodeling. Interestingly, the presence of this AIB1LOW expression signature in breast cancer specimen...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research

Related Links:

Authors: Gomes I, de Almeida BP, Dâmaso S, Mansinho A, Correia I, Henriques S, Cruz-Duarte R, Vilhais G, Félix P, Alves P, Corredeira P, Barbosa-Morais NL, Costa L, Casimiro S Abstract The role of RANKL-RANK pathway in progesterone-driven mammary carcinogenesis and triple negative breast cancer tumorigenesis has been well characterized. However, and despite evidences of the existence of RANK-positive hormone receptor (HR)-positive breast tumors, the implication of RANK expression in HR-positive breast cancers has not been addressed before. Here, we report that RANK pathway affects the expression of cel...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
il;ois Bertucci Exquisitely exploiting defects in homologous recombination process, poly(ADP-ribose) polymerase (PARP) inhibitors have recently emerged as a promising class of therapeutics in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer with germline breast cancer 1 (BRCA1) or breast cancer 2 (BRCA2) mutations (gBRCA1/2m). In this setting, PARP inhibitors, either as single agent or in combination with platinum-based chemotherapy, significantly increased progression-free survival, as compared to conventional chemotherapy. Accordingly, further therapeutic advances are expected at an ear...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Condition:   Breast Cancer Invasive Interventions:   Drug: Pyrotinib;   Drug: Trastuzumab;   Drug: Pertuzumab;   Drug: Nab-paclitaxel;   Drug: EC chemotherapy;   Drug: Physician's choice;   Drug: T-DM1;   Procedure: Surgery Sponsors:   Shanghai Jiao Tong University School of Medicine;   Jiangsu HengRui Medicine Co., Ltd. Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
ConclusionThis study shows that in BC patients with BM treated with SRS, biologic subtype affects LC. Consideration of radiation treatment intensification or altered fractionation to improve LC may be indicated for the TN subtype. Further multicenter studies are necessary to corroborate our results.
Source: Journal of Radiation Oncology - Category: Cancer & Oncology Source Type: research
Condition:   Breast Cancer Invasive Interventions:   Drug: Pyrotinib;   Drug: Trastuzumab;   Drug: Pertuzumab;   Drug: Nab-paclitaxel;   Drug: EC chemotherapy;   Drug: Physician's choice;   Drug: T-DM1;   Procedure: Surgery Sponsors:   Shanghai Jiao Tong University School of Medicine;   Jiangsu HengRui Medicine Co., Ltd. Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Despite improvements in early diagnosis and treatment, breast cancer is still a major health problem worldwide. Among breast cancer subtypes, the most challenging and harder to treat is represented by triple-negative molecular subtype. Due to its intrinsic features this subtype cannot be treated neither with hormonal therapy (since it does not express estrogen or progesterone receptors) nor with epidermal growth factor receptor 2 (HER2) inhibitors (as it does not express high levels of this protein). For these reasons, the standard of care for these patients is represented by a combination of surgery, radiation therapy and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
CONCLUSIONS: A delay in NSC initiation of more than 61 days after BC diagnosis was associated with an increased risk of death. Early initiation of NSC should be a priority; multidisciplinary teams must focus in coordination of care and patient-centered timely treatment planning and delivery. IMPLICATIONS FOR PRACTICE: As we demonstrated that a delay in neoadjuvant systemic chemotherapy initiation of more than 61 days after breast cancer diagnosis is associated with an increased risk of death, efforts must focus on early initiation of therapy, which should be a priority; multidisciplinary teams must enhance coor...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
ConclusionPatients attending the symptomatic breast cancer unit Beaumont Hospital have different demographics compared with the national registry data. This presents particular challenges for management.
Source: Irish Journal of Medical Science - Category: General Medicine Source Type: research
This article will serve as reference guide to pathologists on what we do and why we do the same.
Source: Indian Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
Abstract Triple negative breast cancer (TNBC) is one of the most aggressive subtype of breast cancer accounting for 15-20% of cases and is defined by the lack of hormonal receptors viz., estrogen receptor (ER), progesterone receptor (PR) and expression of human epidermal growth receptor 2 (HER2). Treatment of TNBC is more challenging than other subtypes of breast cancer due to the lack of markers for the molecularly targeted therapies (ER, PR, and HER-2/ Neu), the conventional chemotherapeutic agents are still the mainstay of the therapeutic protocols of its patients. Despite, TNBC being more chemo-responsive than...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research
More News: Breast Cancer | Cancer | Cancer & Oncology | Chemotherapy | Genetics | HER2 | Hormones | Science