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Expression of Type IV Collagenase and Procollagen Genes and Its Correlation with the Tumorigenic, Invasive, and Metastatic Abilities of Oncogene-transformed Human Bronchial Epithelial Cells¹

Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111 [H. U., R. D. B., A. J. P. K-S.], and Laboratory of Human Carcinogenesis, National Cancer Institute, [R. R., A. P., C. C. H.], and Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, [Re. R.], National Institutes of Health, Bethesda, Maryland 20892

In a series of immortalized human bronchial epithelial cell lines contining various oncogenes, the transcriptional levels of the type IV collagenase and the type IV procollagen genes were compared with the properties of invasiveness in vitro and tumorigenicity and metastatic ability in athymic nude mice. v-Ha-ras greatly enhanced invasion and metastasis, whereas v-Ki-ras, c-myc, and c-raf had lesser effects on these malignant phenotypes. In addition, cell lines derived from tumors obtained by injecting the original immortalized human bronchial epithelial cell lines into nude mice exhibited enhanced invasive and metastatic abilities and increased level of type IV collagenase mRNA when compared with the original immortalized human bronchial epithelial cell lines. Invasiveness and metastatic capacity correlated positively with expression of the type IV collagenase gene and negatively with the expression of the type IV procollagen gene, suggesting that these phenotypes are associated both with decreased production and increased dissolution of extracellular matrix.

¹ Supported in part by NIH Grants CA 44981 and CA 06927.

² To whom requests for reprints should be addressed.

Received 2/22/89. Revised 5/ 8/89. Accepted 5/12/89.

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