EXPRESSION OF 67 KDA LAMININ RECEPTOR IN HUMAN BREAST-CANCER CELLS - REGULATION BY PROGESTINS

The level of 67 kDa laminin receptor (67LR) expression on breast and c olon tumor cell surfaces was previously shown to be correlated with th e capacity of tumor cells to metastasize. In the present work we inves tigate the effects of progestins and estrogen on the expression of 67L R in two sublines of the T47D human breast cancer cells: weakly tumori genic, poorly invasive parental T47D cells and a highly tumorigenic, m ore invasive T47Dco subclone. Immunoblotting with an affinity purified antibody directed against a synthetic peptide recognizes the 67LR in these cells. 67LR expression in the T47Dco subclone is 5.5-fold higher than in their parental T47D cells. Treatment of T47D cells with 1 nM of the synthetic progestin R5020 results' in a 4-fold increase in 67LR protein expression. Estrogen also induced 67LR expression, but only b y 1.5-fold. The progestin-stimulated expression of the 67LR correlates with a 4.3-fold increase in attachment of T47D cells to laminin. A mo noclonal antibody, mAb 13, directed against beta1 integrin, completely blocks the attachment of T47D cells to fibronectin, only partially in hibits the attachment of T47D cells to laminin, and appears not to aff ect the progestin-stimulated laminin attachment of T47D cells. A new a ntiprogestin, ZK 112.993, significantly inhibits both progestin-stimul ated 67LR expression and the increased attachment to laminin. These re sults suggest a possible role for progestin in mediating one of the mu ltiple events thought to be important in metastasis of steroid recepto r positive human breast cancer cells.