Pancreatic carcinoma cell lines with SMAD4 inactivation show distinct expression responses to TGFB1.
Transforming growth factor beta-1 (TGFB1)-induced gene expression was studied in five pancreatic carcinoma cell lines and one known TGFB1-sensitive cell line (HaCaT) by use of high-density filter-based cDNA microarrays representing over 4,000 human genes. The results indicate a complex cellular response to TGFB1 with 10% of the investigated genes showing altered expression after 3 or 48 hr of TGFB1 exposure. The tumor cell lines displayed a gradually inversed gene expression pattern, which correlated with reduced sensitivity to TGFB1, as compared to the HaCaT cell line. In the HaCaT cells, several proapoptotic genes showed increased expression in response to TGFB1, whereas the expression of antiapoptotic genes was decreased. In contrast, two pancreatic carcinoma cell lines, previously found to be growth stimulated by TGFB1, displayed an expression pattern opposite to that of these genes. Similarly, the expression of other functional groups of genes, such as cell cycle and transcription factor related genes, was almost completely reversed in these two tumor cell lines. Importantly, three of the five investigated pancreatic carcinoma cell lines responded to TGFB1, although they had SMAD4 inactivations, suggesting that the observed gene expression changes in these cell lines must be accomplished by SMAD-independent pathways.
Jonson
Tord
T
Department of Clinical Genetics, Lund University Hospital, SE-221 85 Lund, Sweden. Tord.Jonson@klingen.lu.se
Heidenblad
Markus
M
Håkansson
Petra
P
Gorunova
Ludmila
L
Johansson
Bertil
B
Fioretos
Thoas
T
Höglund
Mattias
M
D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics; D051901:Smad4 Protein; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D012334:RNA, Neoplasm; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C508960:TGFB1 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1