MOLECULAR-GENETIC ANALYSIS OF TGF-BETA-1 IN BREAST-CANCER

Conflicting data suggest that TGF-beta 1 can either inhibit or promote the progression of breast cancer. To determine the biological role of TGF beta 1 in mammary carcinoma, in this study we examined the gene s tructure, expression and localization of TGF-beta 1 using paraffin-emb edded samples from 32 (27 IDC, 1 ILC, 1 DCIS, 1 ADH) breast lesions. G ene mutations in the region coding for the active protein were investi gated by PCR-SSCP of exons 5, 6, and 7. mRNA-TGF-beta 1 expression and distribution was examined by NISH using cDNA probes generated by RT-P CR and immunohistochemistry. We detected two mutations in exon 6 TGF-b eta 1 from IDC; and TGF beta 1 mRNA and proteins in 28 (87%) of the tu mors. Invasive breast carcinomas had more intense TGF-beta 1 activity than CIS and than normal tissue adjacent to tumor. TGF beta 1 mRNA and proteins were higher at the edge of the tumor than in the center and were also higher in less differentiated breast neoplasms. TGF-beta 1 m RNA transcription and protein levels did not correlate either with TGF -beta 1 exon 6 mutation or type and grade of differentiation of breast tumors. These observations suggest that TGF beta 1 mutations in breas t neoplasms might cause loss or inactivation of the growth inhibitory effects of TGF-beta 1. They also support the proposed role of TGF-beta 1 in the pathogenesis of breast cancer.