title: No compensation in CD44 stem cell marker following BCL-2 suppression by antisense oligonucleotides.
abstract: Antisense oligonucleotides have previously been used to target regulatory proteins in prostate cancer models. We evaluated mono- and bispecific oligonucleotides which comparably suppressed expression of B-cell lymphoma-2 (BCL-2) in LNCaP cells. Cells compensated by suppressing caspase-3 (an apoptosis promoter), and enhancing the expression of androgen receptor and co-activating p300 and interleukin-6 (IL-6) proteins. This suggests that increased androgen sensitivity accompanies BCL-2 suppression with a pattern associated with more advanced tumors. To further evaluate tumor resistance and compensatory mechanisms we evaluated the stem cell-associated CD44 expression and found it to be unaffected by treatment, suggesting that this tumor population is not activated or expanded by suppressive BCL-2 therapy.
authors: Division of Cellular Biology, Hektoen Institute for Medical Research, 2240 West Ogden Avenue, 2'nd floor, Chicago, IL 60612, USA. DrMarv@Prodigy.net
authors: Marvin
authors: M
authors: Rubenstein
authors: Courtney M P
authors: CM
authors: Hollowell
authors: Patrick
authors: P
authors: Guinan
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D020868:Gene Silencing / Q000187:drug effects*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011944:Receptors, Androgen; D050880:p300-CBP Transcription Factors; D053148:Caspase 3