Characterization of the IGF system and analysis of the possible molecular mechanisms leading to IGF-II overexpression in a mesothelioma

Our plain-English summary of Characterization of the IGF system and analysis of the possible molecular mechanisms leading to IGF-II overexpression in a mesothelioma, by D. Hodzic, L. Delacroix, P. Willemsen, et al (Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Métabolisme, 1997).

The study

• Authors: D. Hodzic, L. Delacroix, P. Willemsen, K. Bensbaho, J. Collette, R. Broux, P. Lefèbvre, J.J. Legros, M. Grooteclaes, R. Winkler
• Journal: Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Métabolisme
• Published: 1997;29(11):549-55
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The expression of members of the IGF system in a mesothelioma from a patient suffering from hypoglycemia, in term placenta and HT29 colon adenocarcinoma cells were compared. Very high levels of IGF-II mRNA and protein were detected in the mesothelioma. Moreover, half of the IGF-II protein took the high-molecular-weight form. We also analyzed the parental imprinting status and the promoter usage of the IGF-II gene. Our results showed loss of imprinting (LOI) in the mesothelioma while the imprinting was maintained in HT29 cells, expressing moderate levels of the transcript. Promoter P4 was active in the three tissues we analyzed, whereas IGF-II mRNA transcription from promoter P3 was only detected in the mesothelioma and the placenta, expressing comparably high levels of the transcript. IGF-II gene structure was identical in the analyzed tissues and cells. The type-I receptor mRNA expression was very low in the tumor. IGFBP-2, -4 and -5 mRNAs were detected in the mesothelioma, while IGFBP-2, -3 and -5 transcripts were detected in the placenta. IGFBP-1 and -6 transcripts were not detected.

In plain English

This laboratory study examined the tumor of a single patient, an 88-year-old man with very low blood sugar (hypoglycemia). His pleural tumor was diagnosed as a "fibrous mesothelioma showing no evidence of malignancy." The article gives his work history as about five years as an underground miner and then work as a mason. It does not mention asbestos. The authors compared the tumor with a term placenta and with HT29 colon cancer cells, measuring a growth factor called IGF-II and related molecules. The tumor's level of IGF-II messenger RNA was comparable to that of placenta, and half of its IGF-II protein was in a high-molecular-weight form. Both inherited copies of the IGF-II gene were active in the tumor, which the authors called loss of imprinting. The HT29 cells kept normal imprinting. Promoters P3 and P4 were active in the tumor and placenta, but only P4 in HT29 cells. No gross gene rearrangement was found. Type-I receptor RNA was barely detectable in the tumor. The authors concluded that loss of imprinting might contribute to the high IGF-II production, possibly only in a minor way.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (molecular) analysis of one patient's tumor, compared with a term placenta and the HT29 colon adenocarcinoma cell line
• Who was studied: One 88-year-old man with extrapancreatic tumor hypoglycemia and a pleural tumor of about 1.5 kg, treated in Liege, Belgium. A term placenta and HT29 cells were used for comparison.
• Exposure: The article does not study or mention asbestos exposure. It reports only the patient's work history: underground miner for about five years, then mason.
• Main results:
  • IGF-II mRNA, relative to 18S rRNA, was 23 in placenta, 14 in the mesothelioma and 0.35 in HT29 cells (printed as "0,35").
  • In the mesothelioma, the text gives IGF-II at 29.3 ng/mg of protein, half of it in a high-molecular-weight form. The figure appears to show 229.3; see text problems.
  • Before the tumor was removed, the patient's serum IGF-II was raised to 1316 ng/ml.
  • Both IGF-II alleles were transcribed in the mesothelioma (loss of imprinting). Imprinting was conserved in HT29 cells. The placenta was not informative.
  • Promoters 3 and 4 were used in the mesothelioma and placenta. Only promoter 4 was used in HT29 cells.
  • No gross rearrangement of the IGF-II gene was found in the mesothelioma, compared with placenta and lymphocyte DNA from 5 blood donors.
  • Type-I receptor mRNA was barely detectable in the mesothelioma, while HT29 cells gave a strong signal.
  • In the mesothelioma, IGFBP-2, -4 and -5 mRNAs were detected and IGFBP-1, -3 and -6 were not. IGFBP-3 mRNA was found only in placenta. IGFBP-5 mRNA was about doubled in the mesothelioma.
• The authors' conclusion: The authors concluded that loss of imprinting might contribute to the increased IGF-II transcript in this tumor, though its contribution might only be minor.
• Limitations the authors state:
  • The authors said the contribution of loss of imprinting might be minor, because it usually only doubles the transcription rate.
  • The authors could not tell whether differences from published cell-line results reflected a peculiarity of this one primary tumor or differences between tissue and cultured cells.
  • The authors said the IGF system still needs complete characterization at the protein level. Binding proteins and receptor were measured only as mRNA.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma, Adenocarcinoma.

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