Impact of PTEN on the expression of insulin-like growth factors (IGFs) and IGF-binding proteins in human gastric adenocarcinoma cells

Journal Article · Fri May 13 04:00:00 EDT 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2005.03.045· OSTI ID:20709183

Yi, Ho-Keun ^[1]; Kim, Sun-Young ^[2]; Hwang, Pyoung-Han ^[2]; Kim, Chan-Young ^[3]; Yang, Doo-Hyun ^[3]; Oh, Youngman ^[4]; Lee, Dae-Yeol ^[2]

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1. Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of)
2. Department of Pediatrics, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of)
3. Department of Surgery, Chonbuk National University Medical School, Jeonju (Korea, Republic of)
4. Department of Pathology, School of Medicine, Virginia Commonwealth University, Richmond, VA (United States)

PTEN is a tumor suppressor gene that is frequently mutated or deleted in a variety of human cancers including human gastric cancer. PTEN functions primarily as a lipid phosphatase and plays a key role in the regulation of the PI3 kinase/Akt pathway, thereby modulating cell proliferation and cell survival. On the other hand, the IGF system plays an important role in cell proliferation and cell survival via the PI3 kinase/Akt and MAP kinase pathways in many cancer cells. To characterize the impact of PTEN on the IGF-IGFR-IGFBP axis in gastric cancer, we overexpressed PTEN using an adenovirus gene transfer system in human gastric adenocarcinoma cells, SNU-484 and SNU-663, which lack PTEN. Overexpression of PTEN inhibited serum-induced as well as IGF-I-induced cell proliferation as compared to control cells. PTEN overexpression resulted in a significant decrease in the expression of IGF-I, -II, and IGF-IR. Interestingly, amongst the six IGFBPs, only IGFBP-3 was upregulated by PTEN, whereas IGFBP-4 and -6 were reduced. The IGFBP-3 promoter activity assay and Western immunoblotting demonstrate that PTEN regulates IGFBP-3 at the transcriptional level. In addition, the PI3 kinase inhibitor, LY294002, upregulates IGFBP-3 expression but downregulates IGF-I and IGF-II, indicating that PTEN controls IGFBP-3 and IGFs by an Akt-dependent pathway. These findings suggest that PTEN may inhibit antiapoptotic IGF actions not only by blocking the IGF-IGFR-induced Akt activity, but also by regulating expression of components of the IGF system, in particular, upregulation of IGFBP-3, which is known to exert antiproliferative effects through IGF-dependent and IGF-independent mechanisms in cancer cells.

• OSTI ID: 20709183
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 330; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADENOVIRUS
CARCINOMAS
CELL PROLIFERATION
GENE REGULATION
GROWTH FACTORS
INSULIN
LIPIDS
RECEPTORS