NEOPLASTIC PROGRESSION OF BREAST EPITHELIAL-CELLS - A MOLECULAR ANALYSIS

Molecular changes associated with breast cancer progression were chara cterized using the MCF-10F cell series. MCF-10F was established from f ibrous mastectomy tissue of a patient without detectable cancer. In vi tro treatment of MCF-10F cells with benzo(a)pyrene resulted in a trans formed subclone MCF-10F-BP1 (BP1), Transfection of clone BP1 with T24- Hras resulted in the tumorigenic line MCF-10F-BP1 -Tras (BP1-Tras), Us ing flow cytometry, the expression of HLA I, ERBB-2 and MUC-1 was foun d to be comparable in 'normal' MCF-10F, transformed BP1 and tumorigeni c BP1-Tras cells. Glycosylated mucin is elevated in BP1 but reduced in BP1-Tras cells, Using mRNA differential display analysis, cDNA profil es of the 'normal', transformed and tumorigenic cell lines were striki ngly similar, yet distinct and elevated expression of several common c DNA fragments was detected in BP1 and BP1-Tras when compared with MCF- 10F cells. These fragments were cloned and sequenced. The sequences of clones T1-360 and C4-310 are homologous to two reported EST cDNA clon es from human fetal tissue and were further characterized. Elevated ex pression of the genes corresponding to clones T1-360 and C4-310 was ve rified using Northern blotting. High-level expression of these genes w as also detected in the breast cancer cell line MCF-7 that was derived from the pleural effusion of a patient with advanced breast cancer, T herefore, specific molecular changes associated with breast cancer dev elopment were identified and may be indicators of neoplastic progressi on.