Screening for functional tumor suppressor activity in pancreatic cancer.
Pancreatic cancer has a well-known reputation as one of the leading causes of cancer deaths worldwide. Thus, acquisition of efficient approaches and markers for accurate detection at the earlier stages of the disease should be prioritized. We have been focusing on tumor suppressor genes (TSGs) activity in pancreatic cancer to find effective methods for its genetic diagnosis and/or treatment. In this study, we utilized the technique of micro-cell-mediated chromosome transfer (MMCT) to introduce a normal copy of human chromosome 18 individually into some pancreatic cancer cells. Subsequently, the tumorigenic ability of the resulting hybrids was assessed in vitro and in vivo. In vitro growth of the hybrid clones was significantly delayed as compared to the parental cells. This was paralleled by the hybrid cells promotion of invasive carcinomas in nude mice at a significantly lower rate and with a longer latency than the parental tumor cells. This study provides evidence that MMCT is an efficient tool for screening of tumor suppressor activity in pancreatic cancer. The functional data emerging from this study bring into sharp relief the implication of chromosome 18 as a putative location for new TSG(s), yet to be identified in this region.
3rd Department of Surgery, St. Spiridon University Hospital, Iasi, Romania. llefter@iasi.mednet.ro
Liviu
L
Lefter
Viorel
V
Scripcaru
Makoto
M
Sunamura
Toru
T
Furukawa
Seiki
S
Matsuno
Mitsuo
M
Oshimura
Vasile
V
Drug
Cristian
C
Dragomir
Akira
A
Horii
D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D018014:Gene Transfer Techniques; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics
D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators