Related Experiment Video

Updated: Apr 19, 2026

The Soft Agar Colony Formation Assay
08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

114.6K

Autophagy regulator BECN1 suppresses mammary tumorigenesis driven by WNT1 activation and following parity

Michelle Cicchini1, Rumela Chakrabarti, Sameera Kongara

  • 1a Rutgers Cancer Institute of New Jersey ; New Brunswick , NJ USA.

Autophagy
|December 9, 2014
PubMed

Insights

Monoallelic BECN1 loss promotes mammary tumors in specific contexts, particularly with WNT1 activation. This suggests BECN1 has nonautophagy roles in breast cancer development and progression.

Area of Science:

  • Cancer Biology
  • Molecular Oncology
  • Cellular Signaling

Background:

  • Previous research linked BECN1 deletion to breast cancer, but recent findings question autophagy's tumor-suppressive role.
  • Autophagy-related gene (Atg) defects typically suppress tumorigenesis in mouse models.

Purpose of the Study:

  • To investigate the role of monoallelic BECN1 loss in mammary tumorigenesis.
  • To explore the context-specific effects of BECN1 heterozygosity on tumor development.
  • To elucidate the nonautophagy-related functions of BECN1 in breast cancer.

Main Methods:

  • Utilized mouse models with monoallelic Becn1 loss (Becn1+/-) in specific mammary tumor contexts.
  • Examined tumorigenesis driven by Palb2 loss, ERBB2/PyMT overexpression, parity, and WNT1 activation.
  • Analyzed mammary epithelial cell expansion, TNFRSF11A/RANK signaling, and WNT pathway activation.
  • Correlated findings with human breast cancer data, including BECN1 expression, WNT pathway activity, and prognosis.

Main Results:

  • Monoallelic Becn1 loss did not alter or delayed mammary tumorigenesis in some contexts but promoted it following parity and with WNT1 activation.
  • Becn1 heterozygosity led to immature mammary epithelial cell expansion and aberrant TNFRSF11A/RANK signaling.
  • Low BECN1 expression and activated WNT pathway correlated with triple-negative breast cancer (TNBC), TNFRSF11A axis activation, and poor prognosis in human patients.

Conclusions:

  • BECN1 may possess nonautophagy-related functions crucial for mammary development and tumorigenesis.
  • BECN1 heterozygosity promotes mammary tumors in specific contexts, potentially via immature cell expansion and altered signaling.
  • Findings offer insights into BECN1's paradoxical roles in cancer and inform future research on TNBC pathophysiology and treatment.
Keywords:
8-O-dG, 8-oxo-7, 8-dihydroguanineATG, autophagy-relatedBECN1, Beclin 1, autophagy-relatedBSA, bovine serum albuminBeclin 1CASP3, caspase 3CD24, cluster of differentiation 24DAPI, 4′, 6-diamidino-2-phenylindoleDFS, disease-free survivalDMEM, Dulbecco's modified Eagle's mediumE, 17b-estradiolEGF, epidermal growth factorEGFP, enhanced green fluorescent proteinEGFR/ERBB1, epidermal growth factor receptorEM, electron microscopyEMT, epithelial-to-mesenchymal transitionERBB2, v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2ESR1, estrogen receptor 1FACS, fluorescence activated cell sortingFGF2/bFGF, fibroblast growth factor 2 (basic)GSEA, gene set enrichment analysisH&E, hematoxylin &, eosinHR, hormone receptorIF, immunofluorescenceIHC, immunohistochemistryIL, interleukinITGB1/CD29, Integrin, beta 1 (fibronectin receptor beta polypeptide, antigen CD29 includes MDF2, MSK12)ITGB3/CD61, integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)KRT, keratinKeratin 6LIN−, lineage negative (CD31− CD45− LY76−)LY76/TER119, lymphocyte antigen 76MAP1LC3B/LC3B, microtubule-associated protein 1 light chain 3 betaMEC, mammary epithelial cellMEGM, mammary epithelial growth mediumMGs, mammary glandsMKI67, marker of proliferation Ki-67MMTV, mouse mammary tumor virusMaPC, mammary progenitor cellMaSC, mammary stem cellNFKBNFKB/NFkB, nuclear factor of kappa light polypeptide gene enhancer in B-cellsPBS, phosphate-buffered salinePECAM1/CD31, platelet/endothelial cell adhesion molecule 1PGR, progesterone receptorPI, propidium iodidePTPRC/CD45, protein tyrosine phosphatase, receptor type, CRELA/P65, v-rel avian reticuloendotheliosis viral oncogene homolog aROS, reactive oxygen speciesSD, standard deviationSNPs, single nucleotide polymorphismsSQSTM1/p62, sequestosome1TEBs, terminal end budsTNBCTNBCs, triple-negative breast cancersTNF, tumor necrosis factorTNF11TNFRSF11ATNFRSF11A/TNR11/RANK, tumor necrosis factor receptor superfamily, member 11a, NFKB activatorTNFSF11TNFSF11/TNF11/RANKL, tumor necrosis factor (ligand) superfamily, member 11TNR11TP53 (TRP53 in mice), tumor protein p53 (transformation related protein 53 in mice)WNT1WNT1, wingless-Type MMTV integration site family, member 1basal-like breast canceriMMECs, immortalized mouse mammary epithelial cellsp-KRT8/p-K8, phosphorylated Keratin 8parity

More Related Videos

Mammosphere Assay Reveals Api5-Induced Stemness in Non-Tumorigenic Breast Epithelial Cell Lines07:36

Mammosphere Assay Reveals Api5-Induced Stemness in Non-Tumorigenic Breast Epithelial Cell Lines

Published on: February 24, 2026

204
Modeling Breast Cancer via an Intraductal Injection of Cre-expressing Adenovirus into the Mouse Mammary Gland06:29

Modeling Breast Cancer via an Intraductal Injection of Cre-expressing Adenovirus into the Mouse Mammary Gland

Published on: June 7, 2019

13.6K

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
11.0K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

2.7K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.5K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.6K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.5K