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Tobacco Products, Activin-A, and Lung Cancers

Institution: University of Southern California
Investigator(s): Shao-Yao Ying, Ph.D.
Award Cycle: 1995 (Cycle 4) Grant #: 4IT-0084 Award: $122,583
Subject Area: Pulmonary Disease
Award Type: Inno Dev & Exp Awards (IDEAS)
Abstracts

Initial Award Abstract
Lung cancer is a leading cause of cancer-related deaths which are associated with tobacco smoking. Adverse effects of tobacco smoke on the respiratory cell and cancer risk is well-established, however, the mechanism by which tobacco smoke products initiate uncontrolled cell growth remains to be determined. It is well known that proto-oncogenes and tumor-suppressor genes may coordinate growth factors resulting in unregulated growth such as the development of neoplasia in the lung. Furthermore, inappropriate response to a negative growth factor such as transforming growth factor (TGF) ,8 may result in nepotistic bronchial cell growth. To this end, we have proposed to determine the effect of tobacco product on a member of TGF family, activin-A, as this growth factor may modulate cellular responses to tobacco smoke products in the lung. We propose to examine activin-A in the monocyte/macrophage as a potential etiology of neoplastic development induced by tobacco smoke products.

We plan to explore the potential role of tobacco smoke in affecting activin-A and activin receptors gene expression in pulmonary alveolar macrophage. First, we have examined several monocyte-macrophage cell lines to ascertain that the gene expression of activin-A, and activin receptor in these cell lines is similar to that observed in the lung tissue. The reasons for choosing monocyte/macrophage cell lines as models are based on the fact that one of the monocyte lines secrete activin-A after phorbol ester treatment, suggesting the secretion of activin-A by this cell line is related to cell differentiation. Second, we will determine the effect of a cigarette smoke extract on gene expression of these molecules in monocyte-macrophage cell lines.

So far, we have screened the following cell lines of monocytes, monocytes-macrophage, or macrophage: THP-1 (human monocyte), PU5-1.8 (mouse monocyte-macrophage), P388D1 (mouse monocyte-macrophage), J774A.1 (mouse monocyte-macrophage), and IC-21 (mouse macrophage).

To this day, we have decided to concentrate on THP-1 cells. We have investigated the gene expression for activin-A and activin receptor in this cell line by RT-PCR and in situ hybridization. Now, we are in the process to examine the effects of a cigarette smoke extract on gene expression for activin-A and activin receptor in this monocyte cell line.
Publications

Expression and localization of activin and activin receptors in a human myeloid leukemia cell line, THP-1
Periodical: International Journal of Oncology Index Medicus:
Authors: Ying SY, Zhang Z ART
Yr: 1995 Vol: 6 Nbr: 4 Abs: Pg: 867-870

Expression and localization of activin and activin receptors in a human myeloid leukemia cell line, THP-1
Periodical: International Journal of Oncology Index Medicus:
Authors: Ying SY, Zhang Z ART
Yr: 1995 Vol: 6 Nbr: 4 Abs: Pg: 867-870