Alteration of cell shape, adhesion, and lipid accumulation in human breast cancer cells (T-47D) by human prolactin and growth hormone.
We have demonstrated previously that many human cancer cell lines maintained in tissue culture possess specific cell surface receptors for human prolactin (HPRL) and human growth hormone (HGH). In the present studies, the biological response in vitro of one human breast cancer cell line, T-47D, to the two pituitary hormones was examined. T-47D cells, when grown on tissue culture dishes, display typical epithelioid characteristics; cells are flat and polygonal in shape and are very adhesive to the plastic substratum. Upon the addition of HPRL or HGH (10 to 1000 ng/ml), in the presence of hydrocortisone, insulin, and triiodothyronine, each at 1 microgram/ml, the T-47D cells became round and refractile. In addition, there was a dramatic reduction in the adhesiveness of the cells to the substratum; 80% of the hormone-treated cells were detached by trypsin (25 micrograms/ml) in 30 min at 37 degrees, as compared with 5% for cells not treated with hormones. These prolactin-induced changes could be abolished upon the addition of antiserum to prolactin. Neither HPRL nor the combination of hydrocortisone, insulin, and triiodothyronine alone was active, indicating a synergism between HPRL and hydrocortisone, insulin, and triiodothyronine. It was subsequently found that only hydrocortisone was required for the action of HPRL, and that human luteininzing hormone and ovine growth hormone were inactive, whereas ovine prolactin exerted a very weak effect. In addition, in the presence of hydrocortisone (or hydrocortisone, insulin, and triiodothyronine), HPRL (or HGH) retarded cell proliferation by 30%, whereas HPRL or hydrocortisone by itself had no effect on cell growth. Ultrastructural studies revealed that, accompanying cell rounding and reduced adhesion, HPRL and HGH increased the formation of intracytoplasmic lipid droplets in the T-47D cells. The increase in lipid synthesis was confirmed by the staining of cells with Oil Red O, and by monitoring the incorporation of [14C]acetate into lipid; HPRL stimulated lipid synthesis and accumulation by approximately 2-fold. Thus, receptor-positive human breast cancer cells are biologically responsive in vitro to HPRL and HGH.
D000085:Acetates / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D002250:Carbon Radioisotopes; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D050356:Lipid Metabolism; D008854:Microscopy, Electron; D011388:Prolactin / Q000494:pharmacology*
D000085:Acetates; D002250:Carbon Radioisotopes; D004273:DNA, Neoplasm; D011388:Prolactin; D013006:Growth Hormone