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