Inactivation of TGF-{beta} signaling in lung cancer results in increased CDK4 activity that can be rescued by ELF

Journal Article · Fri Aug 11 00:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.05.195· OSTI ID:20854403

Baek, Hye Jung ^[1]; Kim, Sang Soo ^[1]; Silva, Fabio May da ^[1]; Volpe, Eugene A ^[1]; Evans, Stephen ^[1]; Mishra, Bibhuti ^[1]; Mishra, Lopa ^[2]; Blair Marshall, M ^[1]

---

1. Department of Surgery, Laboratory of Cancer Genetics, Digestive Diseases, and Developmental Molecular Biology, Lombardi Cancer Center, Georgetown University, Washington, DC (United States)
2. Department of Surgery, Laboratory of Cancer Genetics, Digestive Diseases, and Developmental Molecular Biology, Lombardi Cancer Center, Georgetown University, Washington, DC (United States) and Department of Veterans Affairs, Washington, DC (United States)

Escape from TGF-{beta} inhibition of proliferation is a hallmark of multiple cancers including lung cancer. We explored the role of ELF, crucial TGF-{beta} adaptor protein identified from endodermal progenitor cells, in lung carcinogenesis and cell-cycle regulation. Interestingly, elf {sup -/-} mice develop multiple defects that include lung, liver, and cardiac abnormalities. Four out of 6 lung cancer and mesothelioma cell lines displayed deficiency of ELF expression with increased CDK4 expression. Immunohistochemistry and Western blot analysis of primary human lung cancers also showed decreased ELF expression and overexpression of CDK4. Moreover, rescue of ELF in ELF-deficient cell lines decreased the expression of CDK4 and resulted in accumulation of G1/S checkpoint arrested cells. These results suggest that disruption in TGF-{beta} signaling mediated by loss of ELF in lung cancer leads to cell-cycle deregulation by modulating CDK4 and ELF highlights a key role of TGF-{beta} adaptor protein in suppressing early lung cancer.

• OSTI ID: 20854403
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 346, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2006.05.195; PII: S0006-291X(06)01259-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARCINOGENESIS
CARCINOMAS
CELL CYCLE
GENE REGULATION
INACTIVATION
INHIBITION
LIVER
LUNGS
MICE
PROTEINS