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Published on: May 1, 2019
Isoform-specific expression of 14-3-3 proteins in human lung cancer tissues
Wenqing Qi1, Xiaobing Liu, Dianhua Qiao
1Arizona Cancer Center, Department of Cell Biology and Anatomy, The University of Arizona, Tucson, AZ 85724, USA.
Abstract:
14-3-3 Proteins play important roles in a wide range of vital regulatory processes, including signal transduction, apoptosis, cell cycle progression and DNA replication. In mammalian cells, 7 14-3-3 isoforms (beta, gamma, epsilon, eta, sigma, theta and zeta) have been identified and each of these seems to have distinct tissue localizations and isoform-specific functions. Previous studies have shown that 14-3-3 protein levels are higher in human lung cancers as compared to normal tissues. It is unclear, however, which of the 14-3-3 isoform(s) are overexpressed in these cancers. In our study, the levels of all seven 14-3-3 isoforms were examined by RT-PCR and Western blotting. We show that the message for only two isoforms, 14-3-3epsilon and zeta, could be detected in normal tissues. In lung cancer biopsies, however, four isoforms, 14-3-3beta, gamma, sigma, and theta;, in addition to 14-3-3epsilon and zeta, were present in abundance. The expression frequency of 14-3-3beta, gamma, sigma and theta; isoforms was 11, 10, 13 and 8 of the 14 biopsies examined, respectively. The data from immunohistochemical staining and Western blotting were consistent with the RT-PCR results. Given the prevalence of elevated 14-3-3 expression in human lung cancers we propose that these proteins may be involved in lung cancer tumorigenesis and that specific 14-3-3 proteins may be useful as markers for lung cancer diagnosis and targets for therapy.
Insights
Seven 14-3-3 proteins are crucial for cell regulation. This study found four specific 14-3-3 isoforms are overexpressed in lung cancer, suggesting their potential as diagnostic markers and therapeutic targets.
Area of Science:
- Molecular biology
- Cancer research
- Cellular regulation
Background:
- 14-3-3 proteins regulate vital cellular processes like signal transduction and apoptosis.
- Seven 14-3-3 isoforms exist in mammals, with distinct tissue localizations and functions.
- Elevated 14-3-3 protein levels are observed in human lung cancers compared to normal tissues.
Purpose of the Study:
- To identify which specific 14-3-3 isoforms are overexpressed in human lung cancers.
- To investigate the potential role of 14-3-3 isoforms in lung cancer development.
- To evaluate the utility of 14-3-3 isoforms as diagnostic markers and therapeutic targets for lung cancer.
Main Methods:
- Reverse transcription polymerase chain reaction (RT-PCR) to detect mRNA levels of all seven 14-3-3 isoforms.
- Western blotting to confirm protein expression levels.
- Immunohistochemical staining to analyze protein localization and abundance in tissue samples.
Main Results:
- Only 14-3-3epsilon and zeta isoforms were detected in normal tissues.
- Four additional isoforms (14-3-3beta, gamma, sigma, and theta) were found to be highly expressed in lung cancer biopsies.
- Expression frequencies for 14-3-3beta, gamma, sigma, and theta were 11, 10, 13, and 8 out of 14 biopsies, respectively.
- RT-PCR results were corroborated by Western blotting and immunohistochemical staining.
Conclusions:
- The study identified specific 14-3-3 isoforms (beta, gamma, sigma, theta, epsilon, and zeta) that are aberrantly expressed in lung cancer.
- Overexpression of these 14-3-3 isoforms suggests their involvement in lung cancer tumorigenesis.
- Specific 14-3-3 proteins may serve as valuable biomarkers for lung cancer diagnosis and potential targets for novel therapies.