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Implication of a protein-tyrosine-phosphatase in human lung cancer
1INSERM Unité 326, Phospholipides Membranaires, Signalisation Cellulaire et Lipoprotéines, Hôpital Purpan, Toulouse, France.
Abstract:
Protein tyrosyl phosphorylation plays an essential role in regulating cellular events such as proliferation, differentiation and oncogenesis. The recent characterization of the family of protein tyrosine phosphatases (PTPases) suggests that dephosphorylation might be a crucial event in these phenomena. One of the functions of PTPases is to reverse the effect of protein tyrosine kinases (PTKases), many of which are oncogenes, suggesting that they may act as tumor suppressors as described for HPTP gamma. In order to investigate the implication in lung cancer of HPTP beta, a receptor PTPase, we have developed a semi-quantitative method derived from primer-directed reverse transcription (RT) and subsequent polymerase chain reaction (PCR) with 32P-labelled nucleotide. We have demonstrated that the expression of HPTP beta mRNA was dramatically decreased in lung adenocarcinomas and lung malpighian carcinomas as compared to normal lung tissue. In addition, HPTP beta was not expressed in the pulmonar adenocarcinoma cell line A427, which proliferates in a deregulated way. These results suggest that the loss of expression of HPTP beta might play a role in neoplasic transformation and thus this molecule could act as a tumor suppressor factor.
Insights
Reduced expression of receptor protein tyrosine phosphatase beta (HPTP beta) mRNA in lung cancer suggests it may function as a tumor suppressor. Loss of HPTP beta may contribute to neoplastic transformation.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- Protein tyrosyl phosphorylation is crucial for cellular events including proliferation and oncogenesis.
- Protein tyrosine phosphatases (PTPases) counteract protein tyrosine kinases (PTKases), some of which are oncogenes.
- PTPases, like HPTP gamma, may act as tumor suppressors by reversing oncogenic PTKase activity.
Purpose of the Study:
- To investigate the role of the receptor PTPase, HPTP beta, in lung cancer.
- To determine if HPTP beta expression is altered in lung tumor tissues and cell lines.
Main Methods:
- Developed a semi-quantitative method using primer-directed reverse transcription (RT) and 32P-labelled polymerase chain reaction (PCR).
- Analyzed HPTP beta mRNA expression levels in lung adenocarcinomas, lung malpighian carcinomas, and normal lung tissue.
- Assessed HPTP beta expression in the A427 pulmonary adenocarcinoma cell line.
Main Results:
- HPTP beta mRNA expression was significantly decreased in lung adenocarcinomas and malpighian carcinomas compared to normal lung tissue.
- HPTP beta was not expressed in the deregulated A427 pulmonary adenocarcinoma cell line.
- Demonstrated a dramatic reduction in HPTP beta mRNA in lung cancer samples.
Conclusions:
- The loss of HPTP beta expression may play a role in lung cancer development.
- HPTP beta is a potential tumor suppressor factor in lung neoplasia.
- Further research into HPTP beta's function in lung cancer is warranted.