Transgenic human programmed cell death 5 expression in mice suppresses skin cancer development by enhancing apoptosis.

Abstract

AIMS:

We sought to probe the role of human programmed cell death 5 (PDCD5) in vivo and to understand its mechanisms.

MAIN METHODS:

A transgenic mouse model of human PDCD5 was generated by pronuclear microinjection. Apoptosis in tissues of three independent transgenic mouse lines was quantified by terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL) and compared to wild type littermates. Their lifespan was compared. 8-Week PDCD5 mice and wild type mice (at a group of 5) were treated with carcinogen 3-methylcholanthrene (3-MC) at 5 μg per week to induce skin cancer. Cancer development was measured by examining hematoxylin and eosin (H&E) stained skin sections after 5 weeks and 10 weeks treatment. Protein expression was determined by Western blot and apoptosis of skin cells was quantified by TUNEL.

KEY FINDINGS:

Starting from 5 months after birth, significant autonomous apoptosis was observed in multiple tissues of transgenic mice including skin, liver, spleen, adrenal gland and thyroid gland comparing to their wild type littermates. The average lifespan of PDCD5 mice was reduced to 9.75 months (normally 24-30 months). Moreover, carcinogen 3-MC induced skin cancer development was attenuated in the lesion of PDCD5 transgenic mice by enhancing apoptosis. Pro-apoptotic protein Bax expression was up-regulated in the 3-MC treated skin of transgenic mice.

SIGNIFICANCE:

These results suggest PDCD5 plays an antitumor role by enhancing apoptosis in animal physiological settings. Therefore, PDCD5 is a potential target for cancer therapy.

• Authors: Yanhui Li, Gang Zhou, Lijun La, Xiaochun Chi, Ye Cao, Jing Liu, Zhanhui Zhang, Yingyu Chen, Baiyan Wu
• Journal: Life sciences (Life Sci) Vol. 92 Issue 24-26 Pg. 1208-14 (Jul 10 2013) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 23688867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• Neoplasm Proteins
• PDCD5 protein, human

Topics

• Animals
• Apoptosis (genetics)
• Apoptosis Regulatory Proteins (biosynthesis, genetics)
• Cell Death (genetics)
• Down-Regulation (genetics)
• Humans
• Mice
• Mice, Transgenic
• Neoplasm Proteins (biosynthesis, genetics)
• Random Allocation
• Skin Neoplasms (genetics, pathology, prevention & control)
• Up-Regulation (genetics)