{"id":"14f1c462-6982-55d4-891c-7400f178d1fc","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-eralpha-proliferation","predicate":"increases_at_10_micromolar","statement":"DIM at 10 micromolar increased proliferation in estrogen-deprived breast-cancer cells; an ERalpha antagonist blocked the response.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"285fdef0-bc51-5635-b9f4-cca028906296","mechanism_event_label":"A growth-promoting response appeared under one defined hormonal condition.","subject":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"object":{"id":"d3daee2b-acdd-5fc7-b96d-4439bda86b74","slug":"cell-proliferation","display_name":"Cell proliferation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"285fdef0-bc51-5635-b9f4-cca028906296","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-eralpha-proliferation-event","event_type":"biochemical_relationship","label":"A growth-promoting response appeared under one defined hormonal condition.","description":"DIM at 10 micromolar increased proliferation in estrogen-deprived breast-cancer cells; an ERalpha antagonist blocked the response.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b03c0784-d18d-58e3-99c5-2bcfed07028b","slug":"esr1","display_name":"Human estrogen receptor alpha / ESR1","entity_type_key":"protein"},"role":"mediator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8a263735-8138-5596-8687-6f47450bf011","slug":"fulvestrant","display_name":"Fulvestrant / ICI 182780","entity_type_key":"small_molecule"},"role":"blocking_control","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d3daee2b-acdd-5fc7-b96d-4439bda86b74","slug":"cell-proliferation","display_name":"Cell proliferation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/25048790.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17\", \"start_char\": 0, \"end_char\": 1824, \"text_sha256\": \"3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Gene expression, chromatin, inhibitors and growth assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"DIM 10 versus 50 micromolar; estradiol absent","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human MCF-7 and T47D cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A growth-promoting response appeared under one defined hormonal condition.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"ERalpha and proliferation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"c37cc595-57cd-5403-b864-75b5585a264e","evidence_kind":"source_excerpt","locator":"Lines 610-621","start_line":610,"end_line":621,"excerpt":"### dim-eralpha-proliferation\nDIM at 10 micromolar increased proliferation in estrogen-deprived breast-cancer cells; an ERalpha antagonist blocked the response.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A growth-promoting response appeared under one defined hormonal condition.\norganism: Human MCF-7 and T47D cells\ntissue_or_cell_type: ERalpha and proliferation\nexperimental_model: Gene expression, chromatin, inhibitors and growth assays\nlimitations: The authors call 10 micromolar obtainable, but this is not a demonstrated human tissue concentration or clinical tumor outcome. Estrogen context and concentration matter.\nexposure: DIM 10 versus 50 micromolar; estradiol absent\nevidence_span: {\"source_cache\": \"artifacts/dim-research/25048790.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17\", \"start_char\": 0, \"end_char\": 1824, \"text_sha256\": \"3729748e0cd55782230ad119eddfb3a79e0cdfd78503f5dbf397ae0ab5f68a17\"}\n[dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524","model_system":"Gene expression, chromatin, inhibitors and growth assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dim-p25048790] Low levels of 3,3'-diindolylmethane activate estrogen receptor α and induce proliferation of breast cancer cells in the absence of estradiol. (2014). https://pubmed.ncbi.nlm.nih.gov/25048790/ DOI: 10.1186/1471-2407-14-524","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b6d70682-97f9-5893-a03c-f9f88836033c","stable_key":"import-182336c6-ed36-5ec6-8a09-25c31096262e","title":"Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"31e14060de904976d2f5d439f2bc9c8a99a72d34626c562c78429025e050d404","revision_id":"611094c1-a9cf-5b9b-b255-ac70b571696a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}