Therapeutic radiation induces different changes in expression profiles of metallothionein (MT) mRNA, MT protein, Ki 67 and minichromosome maintenance protein 3 in human rectal adenocarcinoma.

Abstract

AIM:

The study aimed at the evaluation of the effects of radiotherapy on expression of metallothionein (MT) isoforms, both in the form of quantitative alterations in mRNA, and differences in expression of MTI/II proteins in rectal tumours.

MATERIALS AND METHODS:

Material for the study originated from 21 patients with rectal cancer at stage II or III. Material for immunohistochemical studies [MTI/II, Minichromosome Maintenance Protein 3 (MCM3), Ki-67] and real-time polymerase chain reaction (PCR) (mRNA of MT1F, MT1X and MT2A) was sampled twice: during rectoscopic examination before the start of the preoperative radiotherapy (samples A) and from the post operative specimen, following radiotherapy (samples B).

RESULTS:

The level of mRNA expression for each of the studied MT isoforms was higher in cancer cells subjected to irradiation. The most extensive differences were observed for the MT2A isoforms (p=0.09). No differences were disclosed between samples A and B in expression of MT I/II protein. The material sampled after radiotherapy manifested a tendency for reduced proliferative activity of the tumour cells: the decrease of MCM3 expression was significant (p=0.022), while in the case of Ki-67, the difference approached statistical significance (p=0.096).

CONCLUSION:

Application of radiotherapy to rectal adenocarcinoma cells is followed by an increase in MT mRNA expression level, affecting first of all the MT2A isoform. However, we failed to note an increased expression of MTI/II protein coded by the gene. Moreover, application of radiotherapy was followed by a decrease in expression of MCM3 protein. Our results cannot clearly confirm induction of MT after irradiation of human adenocarcinoma cells. The role of MT in radioprotection remains ambiguous.

• Authors: Jolanta Szelachowska, Piotr Dziegiel, Radoslaw Tarkowski, Agnieszka Gomulkiewicz, Marek Bebenek, Agnieszka Halon, Krzysztof Fortuna, Andrzej Wojnar, Jan Kornafel, Rafal Matkowski
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 12 Pg. 5291-7 (Dec 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 23225429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• DNA-Binding Proteins
• Ki-67 Antigen
• MCM3 protein, human
• Nuclear Proteins
• Protein Isoforms
• RNA, Messenger
• Metallothionein
• Minichromosome Maintenance Complex Component 3

Topics

• Adenocarcinoma (genetics, metabolism, pathology, radiotherapy)
• Aged
• Aged, 80 and over
• Cell Cycle Proteins (biosynthesis, genetics)
• DNA-Binding Proteins (biosynthesis, genetics)
• Female
• Gene Expression (radiation effects)
• Gene Expression Profiling
• Humans
• Immunohistochemistry
• Ki-67 Antigen (biosynthesis, genetics)
• Male
• Metallothionein (biosynthesis, genetics)
• Middle Aged
• Minichromosome Maintenance Complex Component 3
• Nuclear Proteins (biosynthesis, genetics)
• Protein Isoforms (biosynthesis, radiation effects)
• RNA, Messenger (biosynthesis, genetics)
• Real-Time Polymerase Chain Reaction
• Rectal Neoplasms (genetics, metabolism, pathology, radiotherapy)