title: Tissue and serum microRNAs in the Kras(G12D) transgenic animal model and in patients with pancreatic cancer.
abstract: microRNAs (miRs) modulate the expression levels of mRNAs and proteins and can thus contribute to cancer initiation and progression. In addition to their intracelluar function, miRs are released from cells and shed into the circulation. We postulated that circulating miRs could provide insight into pathways altered during cancer progression and may indicate responses to treatment. Here we focus on pancreatic cancer malignant progression. We report that changes in miR expression patterns during progression of normal tissues to invasive pancreatic adenocarcinoma in the p48-Cre/LSL-Kras(G12D) mouse model mirrors the miR changes observed in human pancreatic cancer tissues. miR-148a/b and miR-375 expression were found decreased whereas miR-10, miR-21, miR-100 and miR-155 were increased when comparing normal tissues, premalignant lesions and invasive carcinoma in the mouse model. Predicted target mRNAs FGFR1 (miR-10) and MLH1 (miR-155) were found downregulated. Quantitation of nine microRNAs in plasma samples from patients distinguished pancreatic cancers from other cancers as well as non-cancerous pancreatic disease. Finally, gemcitabine treatment of control animals and p48-Cre/LSL-Kras(G12D) animals with pancreatic cancer caused distinct and up to 60-fold changes in circulating miRs that indicate differential drug effects on normal and cancer tissues. These findings support the significance of detecting miRs in the circulation and suggests that circulating miRs could serve as indicators of drug response.
authors: Lombardi Cancer Center, Georgetown University, Washington, DC, United States of America.
authors: Joseph J
authors: JJ
authors: LaConti
authors: Narayan
authors: N
authors: Shivapurkar
authors: Anju
authors: A
authors: Preet
authors: Anne
authors: A
authors: Deslattes Mays
authors: Ivana
authors: I
authors: Peran
authors: Sung Eun
authors: SE
authors: Kim
authors: John L
authors: JL
authors: Marshall
authors: Anna T
authors: AT
authors: Riegel
authors: Anton
authors: A
authors: Wellstein
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D035683:MicroRNAs; D003841:Deoxycytidine; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras); D000093542:Gemcitabine