The nuclear coactivator amplified in breast cancer 1 maintains tumor-initiating cells during development of ductal carcinoma in situ

Ory, Virginie; Tassi, Elena; Cavalli, Luciane R.; Sharif, Ghada M.; Sáenz, Francisco Herrera; Baker, Tabari; Schmidt, Marcel; Mueller, SC; Furth, PA; Wellstein, Anton

doi:10.1038/onc.2013.263

Cited by 18 publications

(36 citation statements)

References 42 publications

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“…All of these genes have previously been implicated in breast cancer pathogenesis, and NCOA3 has recently been shown to be a critical gene in the development and maintenance of DCIS. 35 The allelic imbalance identified on chromosome 10 was somewhat complex. The signal was strongest on the p arm, where cases had gains (3 nonrecurrent, 7 recurrent), losses (1 non-recurrent, 3 recurrent) and copy number neutral allelic imbalance (3 recurrent).…”

Section: Discussionmentioning

confidence: 99%

Copy number analysis of ductal carcinoma in situ with and without recurrence

et al. 2015

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Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer and a frequent mammographic finding requiring treatment. Up to 25% of DCIS can recur and half of recurrences are invasive, but there are no reliable biomarkers for recurrence. We hypothesised that copy number aberrations could predict likelihood of recurrence. We analysed a cohort of pure DCIS cases treated only with wide local excision for genome-wide copy number and loss of heterozygosity using Affymetrix OncoScan MIP arrays. Cases included those without recurrence within 7 years (n = 25) and with recurrence between 1 and 5 years after diagnosis (n = 15). Pure DCIS were broadly similar in copy number changes compared with invasive breast cancer, with the consistent exception of a greater frequency of ERBB2 amplification in DCIS. There were no significant differences in age or ER status between the cases with a recurrence vs those without. Overall, the DCIS cases with recurrence had more copy number events than the DCIS without recurrence. The increased copy number appeared non-random with several genomic regions showing an increase in frequency in recurrent cases, including 20q gain, ERBB2 amplification and 15q loss. Copy number changes may provide prognostic information for DCIS recurrence, but validation in additional cohorts is required. Modern Pathology (2015Pathology ( ) 28, 1174Pathology ( -1184 doi:10.1038/modpathol.2015 published online 19 June 2015 Ductal carcinoma in situ (DCIS) is a proliferation of malignant cells within breast ducts without invasion through the basement membrane. A number of lines of evidence demonstrate that DCIS is a non-obligate precursor of invasive breast cancer, including the natural history of untreated DCIS, 1 the high risk of ipsilateral invasive breast cancer after a diagnosis of DCIS and the common clonal genetic events found in DCIS and synchronous or recurrent invasive breast cancer. 2 Prior to population-based screening mammography, DCIS was an unusual finding comprising only 3-5% of all breast neoplasms. Currently,~20% of cases of screen-detected breast neoplasia are DCIS. 3 Standard treatment has become wide local excision of DCIS with or without adjuvant radiotherapy. 4 Recent clinical trials have found that~25% of DCIS treated with local excision only will recur within 15 years, with the greatest risk of recurrence in the first 5 years. 5 Approximately half of the recurrences will be invasive carcinoma, requiring more extensive treatment, and with a possible decrease in disease-specific survival. 6 Radiotherapy reduces the recurrence rate by about 50%, so despite the fact that only small a small proportion of patients will benefit, many clinicians recommend radiotherapy because of the implications of invasive recurrence. The most commonly used predictive models to estimate the recurrence risk with or without radiotherapy include DCIS grade, tumour size, width

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Section: Discussionmentioning

confidence: 99%

Copy number analysis of ductal carcinoma in situ with and without recurrence

et al. 2015

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“…MCF10A and MCFDCIS [6] cell lines were maintained in DMEM:F12 (Invitrogen, Carlsbad, CA) with 5% horse serum, 20 ng/ml EGF, 0.5 mg/ml hydrocortisone, 100 ng/ml cholera toxin, and 10 lg/ml insulin. MCF10A and MCFDCIS [6] cell lines were maintained in DMEM:F12 (Invitrogen, Carlsbad, CA) with 5% horse serum, 20 ng/ml EGF, 0.5 mg/ml hydrocortisone, 100 ng/ml cholera toxin, and 10 lg/ml insulin.…”

Section: Methodsmentioning

confidence: 99%

“…Further, synergistic interactions of YAP/TAZ and AIB1 at TEAD-binding sites have been described in select cancers [16] but whether interactions of these coactivators with the transcription factor TEAD play a role in the development and progression of TNBC is not known. For this, we performed a series of co-immunoprecipitations (Co-IP) in extracts from the immortalized normal mammary epithelial MCF10A cell line [24] as well as from the MCFDCIS cell line, which is capable of forming DCIS lesions that progress to invasive breast cancer in vivo [6,25,26]. For this, we performed a series of co-immunoprecipitations (Co-IP) in extracts from the immortalized normal mammary epithelial MCF10A cell line [24] as well as from the MCFDCIS cell line, which is capable of forming DCIS lesions that progress to invasive breast cancer in vivo [6,25,26].…”

Section: Aib1 Regulates Induction and Repression Of Subsets Of Yap-tementioning

confidence: 99%

“…The MCF10A cell line is non-tumorigenic when implanted in mice ( Fig EV4G); however, the MCFDCIS cell line forms DCIS lesions that progress to locally invasive triple-negative breast cancer in athymic nude mice over a defined timeline [6,26,58]. The MCF10A cell line is non-tumorigenic when implanted in mice ( Fig EV4G); however, the MCFDCIS cell line forms DCIS lesions that progress to locally invasive triple-negative breast cancer in athymic nude mice over a defined timeline [6,26,58].…”

Section: Aib1-yap Co-activation and Loss Of Anco1 Repression Promote mentioning

confidence: 99%

“…To investigate this, we first asked whether AIB1, YAP/TAZ, and TEAD complexes exist in normal mammary epithelial as well as early-stage breast cancer cells. For this, we performed a series of co-immunoprecipitations (Co-IP) in extracts from the immortalized normal mammary epithelial MCF10A cell line [24] as well as from the MCFDCIS cell line, which is capable of forming DCIS lesions that progress to invasive breast cancer in vivo [6,25,26]. Immunoprecipitation with a pan-TEAD, AIB1, or a YAP/TAZ antibody of endogenous proteins confirmed that robust complexes involving AIB1, YAP/TAZ, and TEAD can be detected in extracts from MCF10A or MCFDCIS cells ( Fig EV1A).…”

Section: Aib1 Regulates Induction and Repression Of Subsets Of Yap-tementioning

confidence: 99%

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Loss of ANCO1 repression at AIB1/YAP targets drives breast cancer progression

et al. 2019

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Transcription factors critical for the transition of normal breast epithelium to ductal carcinoma in situ (DCIS) and invasive breast cancer are not clearly defined. Here, we report that the expression of a subset of YAP-activated and YAP-repressed genes in normal mammary and early-stage breast cancer cells is dependent on the nuclear co-activator AIB1. Gene expression, sequential ChIP, and ChIP-seq analyses show that AIB1 and YAP converge upon TEAD for transcriptional activation and repression. We find that AIB1-YAP repression of genes at the 1q21.3 locus is mediated by AIB1-dependent recruitment of ANCO1, a tumor suppressor whose expression is progressively lost during breast cancer progression. Reducing ANCO1 reverts AIB1-YAPdependent repression, increases cell size, and enhances YAPdriven aberrant 3D growth. Loss of endogenous ANCO1 occurs during DCIS xenograft progression, a pattern associated with poor prognosis in human breast cancer. We conclude that increased expression of AIB1-YAP co-activated targets coupled with a loss of normal ANCO1 repression is critical to patterns of gene expression that mediate malignant progression of earlystage breast cancer.

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AIB1 is a novel target of the high‐risk HPV E6 protein and a biomarker of cervical cancer progression

Miller

Dakić

Spurgeon

et al. 2022

Journal of Medical Virology

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The high-risk human papillomaviruses (HPV-16, -18) are critical etiologic agents in human malignancy, most importantly in cervical cancer. These oncogenic viruses encode the E6 and E7 proteins that are uniformly retained and expressed in cervical cancers and required for maintenance of the tumorigenic phenotype. The E6 and E7 proteins were first identified as targeting the p53 and pRB tumor suppressor pathways, respectively, in host cells, thereby leading to disruption of cell cycle controls. In addition to p53 degradation, a number of other functions and critical targets for E6 have been described, including telomerase, Myc, PDZ-containing proteins, Akt, Wnt, mTORC1, as well as others. In this study, we identified Amplified in Breast Cancer 1 (AIB1) as a new E6 target. We first found that E6 and hTERT altered similar profiling of gene expression in human foreskin keratinocytes (HFK), independent of telomerase activity. Importantly, AIB1 was a common transcriptional target of both E6 and hTERT. We then verified that high-risk E6 but not low-risk E6 expression led to increases in AIB1 transcript levels by real-time RT-PCR, suggesting that AIB1 upregulation may play an important role in cancer development. Western blots demonstrated that AIB1 expression increased in HPV-16 E6 and E7 expressing (E6E7) immortalized foreskin and cervical keratinocytes, and in three of four common cervical cancer cell lines as well. Then, we evaluated the expression of AIB1 in human cervical lesions and invasive carcinoma using immunohistochemical staining. Strikingly, AIB1 showed positivity in the nucleus of cells in the immediate suprabasal epithelium, while nuclei of the basal epithelium were negative, as evident in the Cervical Intraepithelial Neoplasia 1 (CIN1) samples. As the pathological grading of cervical lesions increased from CIN1, CIN2, CIN3 carcinoma in situ and invasive carcinoma, AIB1 staining increased progressively, suggesting that AIB1 may serve as a novel histological biomarker for cervical cancer development. For cases of invasive cervical carcinoma, AIB1 staining was specific to cancerous lesions.Increased expression of AIB1 was also observed in transgenic mouse cervical

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The nuclear coactivator amplified in breast cancer 1 maintains tumor-initiating cells during development of ductal carcinoma in situ

Cited by 18 publications

References 42 publications

Copy number analysis of ductal carcinoma in situ with and without recurrence

Copy number analysis of ductal carcinoma in situ with and without recurrence

Loss of ANCO1 repression at AIB1/YAP targets drives breast cancer progression

AIB1 is a novel target of the high‐risk HPV E6 protein and a biomarker of cervical cancer progression

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