title: Abcc10 status affects mammary tumour growth, metastasis, and docetaxel treatment response.
abstract: BACKGROUND
  Resistance to chemotherapeutic agents is a major obstacle to cancer treatment. A group of ABC efflux pumps, the Multidrug Resistance Proteins, is a source of resistance. Herein, we investigated the role of ABCC10 in mammary tumours, given the important role we have defined for ABCC10 in transporting taxanes, and the recognition that some ABCC proteins have roles in tumour growth.
  
  
  METHODS
  ABCC10 expression was correlated to human breast cancer subtype using breast tissue microarrays. Real-time quantitative PCR and western blot analysis were used to examine ABCC10 expression in human breast cancer lines. Abcc10(-/-) mice were crossed to MMTV-PyVmT mice to produce Abcc10(-/-) vs Abcc10(+/+) mammary tumours and derivative cell lines. We used allograft and cellular assays to perform baseline and drug sensitization analysis of tumours and cell lines.
  
  
  RESULTS
  Clinical sample analyses indicated that ABCC10 was more highly expressed in Her2+ and ER+ than in Her2-, ER-, and triple-negative breast cancer. Unexpectedly, PyVmT; Abcc10(-/-) tumours grew more rapidly than PyVmT; Abcc10(+/+) tumours and were associated with significantly reduced apoptosis and metastasis. PyVmT; Abcc10(-/-) lines were less migratory than PyVmT; Abcc10(+/+) lines. Finally, we showed increased survival of docetaxel-treated MMTV-PyVmT; Abcc10(-/-) mice compared with wild-type mice.
  
  
  CONCLUSIONS
  These data identify roles for Abcc10 in breast cancer pathogenesis and in vivo docetaxel resistance.
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Domanitskaya
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wangari-Talbot
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jacobs
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Peiffer
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Mahdaviyeh
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Paulose
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Malofeeva
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Foster
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: K Q
authors.initials: KQ
authors.lastname: Cai
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Egleston
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, Philadelphia 19111, PA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hopper-Borge
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D046888:Tissue Array Analysis; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D000077143:Docetaxel; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D043823:Taxoids; C421142:ABCC10 protein, human; C508053:ERBB2 protein, human