Ye. Shi et al., EXPRESSION OF 67 KDA LAMININ RECEPTOR IN HUMAN BREAST-CANCER CELLS - REGULATION BY PROGESTINS, Clinical & experimental metastasis, 11(3), 1993, pp. 251-261
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.