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 colon tumor cell surfaces was previously shown to be correlated with the capacity of tumor cells to metastasize. In the present work we investigate the effects of progestins and estrogen on the expression of 67LR in two sublines of the T47D human breast cancer cells: weakly tumorigenic, poorly invasive parental T47D cells and a highly tumorigenic, more 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 by 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 monoclonal antibody, mAb 13, directed against beta 1 integrin, completely blocks the attachment of T47D cells to fibronectin, only partially inhibits the attachment of T47D cells to laminin, and appears not to affect the progestin-stimulated laminin attachment of T47D cells. A new antiprogestin, ZK 112.993, significantly inhibits both progestin-stimulated 67LR expression and the increased attachment to laminin. These results suggest a possible role for progestin in mediating one of the multiple events thought to be important in metastasis of steroid receptor positive human breast cancer cells.
Shi
Y E
YE
Vincent T. Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC 20007.
Torri
J
J
Yieh
L
L
Sobel
M E
ME
Yamada
Y
Y
Lippman
M E
ME
Dickson
R B
RB
Thompson
E W
EW
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001485:Basement Membrane / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D015735:Mifepristone / Q000031:analogs & derivatives / Q000494:pharmacology; D009362:Neoplasm Metastasis; D011397:Promegestone / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D017474:Receptors, Laminin / Q000096:biosynthesis* / Q000187:drug effects; D015203:Reproducibility of Results; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000970:Antineoplastic Agents; D005353:Fibronectins; D007797:Laminin; D017474:Receptors, Laminin; C064879:ZK 112993; D015735:Mifepristone; D011397:Promegestone