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Pancreatic carcinoma cell lines with SMAD4 inactivation show distinct expression responses to TGFB1
Tord Jonson1, Markus Heidenblad, Petra Håkansson
1Department of Clinical Genetics, Lund University Hospital, SE-221 85 Lund, Sweden. Tord.Jonson@klingen.lu.se
Abstract:
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.
Insights
Transforming growth factor beta-1 (TGFB1) alters gene expression in pancreatic cancer cells, revealing complex responses and SMAD-independent pathways. Tumor cells show reduced TGFB1 sensitivity compared to normal cells.
Area of Science:
- Molecular Biology
- Cancer Research
- Genomics
Background:
- Transforming growth factor beta-1 (TGFB1) is a key regulator of cellular processes.
- Pancreatic carcinoma exhibits complex responses to TGFB1, impacting gene expression.
- Understanding TGFB1 signaling is crucial for cancer therapy.
Purpose of the Study:
- To investigate TGFB1-induced gene expression changes in pancreatic carcinoma cell lines.
- To compare TGFB1 response in tumor cells versus a TGFB1-sensitive cell line (HaCaT).
- To explore the role of SMAD-dependent and -independent pathways in TGFB1 response.
Main Methods:
- Utilized high-density filter-based cDNA microarrays for gene expression profiling.
- Analyzed over 4,000 human genes in five pancreatic carcinoma cell lines and HaCaT cells.
- Assessed gene expression changes after 3 and 48 hours of TGFB1 exposure.
Main Results:
- TGFB1 induced significant gene expression alterations in 10% of studied genes.
- Pancreatic tumor cell lines showed an inverse gene expression pattern compared to HaCaT cells, indicating reduced sensitivity.
- HaCaT cells exhibited increased proapoptotic and decreased antiapoptotic gene expression, while two tumor lines showed the opposite pattern.
- SMAD4-inactivated pancreatic cancer cells responded to TGFB1, suggesting SMAD-independent signaling.
Conclusions:
- Pancreatic cancer cells display a complex and often reversed gene expression response to TGFB1 compared to normal cells.
- TGFB1-induced gene expression changes in some pancreatic cancer cells occur via SMAD-independent pathways.
- These findings highlight the intricate role of TGFB1 in pancreatic cancer and suggest potential therapeutic targets.
