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AKT-1, -2, and -3 are expressed in both normal and tumor tissues of the lung, breast, prostate, and colon
M J Zinda1, M A Johnson, J D Paul
1Cancer Research Division, Lilly Research Labs, Eli Lilly and Company, Lilly Corporate Center DC 0546, Indianapolis, IN 46285, USA.
Purpose:
The AKT/PKB kinase controls many of the intracellular processes that are dysregulated in human cancer, including the suppression of apoptosis and anoikis and the induction of cell cycle progression. Three isoforms of AKT have been identified: AKT-1, -2, and -3. Selective up-regulation of AKT-3 RNA expression has been reported in hormone-independent breast and prostate cancer cell lines suggesting that AKT-3 expression may be increased with breast or prostate tumor progression. To determine whether AKT-3 RNA expression is selectively up-regulated in human cancers and whether the patterns of AKT RNA expression may change with tumor development, we examined AKT isoform expression by RT-PCR in human cancer cell lines, primary human cancers, and normal human tissues.
Experimental Design:
AKT-1, -2, and -3 RNA expression was examined by RT-PCR. Because up-regulated AKT-3 expression has been implicated in human breast and prostate cancer progression, we also examined AKT-3 expression levels by semiquantitative RT-PCR using matched normal/tumor first-strand cDNA pairs from colon, breast, prostate, and lung cancers.
Results:
Our data reveal that the overwhelming majority of both normal and tumor tissues express all three of the AKT isoforms. Moreover, semiquantitative RT-PCR of matched normal/tumor pairs confirmed similar AKT-3 RNA expression levels in both normal and tumor tissue.
Conclusions:
Our data show that both normal and tumor tissues express all three of the AKT isoforms and indicate that tumorigenesis does not involve a dramatic shift in the RNA expression patterns of the three AKT isoforms.
Insights
This study found that all three AKT isoforms are expressed in both normal and cancerous human tissues. Tumorigenesis does not appear to involve significant changes in AKT RNA expression patterns.
Area of Science:
- Molecular biology
- Oncology
- Gene expression analysis
Background:
- The AKT/PKB kinase pathway regulates critical cellular processes, including apoptosis, anoikis, and cell cycle progression, which are often dysregulated in human cancers.
- Three AKT isoforms (AKT-1, -2, and -3) have been identified, with AKT-3 RNA expression previously suggested to be selectively upregulated in hormone-independent breast and prostate cancer cell lines, implying a role in tumor progression.
Purpose of the Study:
- To investigate whether AKT-3 RNA expression is selectively upregulated in human cancers.
- To determine if AKT RNA expression patterns change during tumor development.
- To examine AKT isoform expression across various human cancer cell lines, primary cancers, and normal tissues.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) was employed to assess AKT-1, -2, and -3 RNA expression.
- Semiquantitative RT-PCR was specifically used to analyze AKT-3 expression levels in matched normal and tumor tissue pairs from colon, breast, prostate, and lung cancers.
Main Results:
- All three AKT isoforms (AKT-1, -2, and -3) were found to be expressed in the vast majority of both normal and tumor tissues examined.
- Semiquantitative RT-PCR analysis of matched normal/tumor pairs revealed comparable AKT-3 RNA expression levels between normal and cancerous tissues.
Conclusions:
- The findings indicate that tumorigenesis does not involve a substantial alteration in the RNA expression patterns of the three AKT isoforms.
- Both normal and tumor tissues consistently express all three AKT isoforms, suggesting a ubiquitous role for these genes rather than specific upregulation in cancer progression.
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