A survey of human breast cancer sensitivity to growth inhibition by calmodulin antagonists in tissue culture.
We compared the ability of N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide (W-13), a calmodulin antagonist, to inhibit the growth of seven human breast cancer cell lines in tissue culture, to determine whether drug sensitivity was related to estrogen receptor (ER) status, tamoxifen resistance (tamr), or levels of calmodulin activity. We examined three ER+ (estrogen receptor-positive) cell lines (MCF-7, ZR-75-1B, and T47D), two ER+/tamr lines (LY2 and RR), and two ER- (estrogen receptor-negative) cell lines (MDA-MB-231 and MDA-MB-435). There was no difference in the inhibition of cell growth by W-13 in MCF-7 cells and the two tamr MCF-7 cell derivatives, LY2 and RR. In addition, the sensitivity to W-13 did not appear to be related to ER status. Although the mean Ki of the five ER+ cell lines (31 microM) was somewhat higher than the mean Ki of the two ER- cell lines (23 microM), the two cell lines most sensitive to W-13 were the ER+ T47D cells (Ki 15 microM) and the ER- MDA-MB-435 cells (Ki 10 microM). Calmodulin activity was measured in three representative cell lines, MCF-7, LY2, and MDA-MB-435. Calmodulin levels were higher in the most sensitive cell line (MDA-MB-435, 2.7 ng calmodulin/micrograms protein) than in the two less sensitive cell lines, MCF-7 and LY2 (1.3 and 1.6 ng calmodulin/micrograms protein, respectively). However, the MCF-7, LY2, and MDA-MB-435 cells were equally sensitive to another specific calmodulin antagonist, calmidazolium. We conclude that neither ER status, tamoxifen resistance, nor levels of calmodulin activity predict the sensitivity of human breast cancer cell lines to growth inhibition in tissue culture by calmodulin antagonists.
Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506-9223.
J S
JS
Strobl
V A
VA
Peterson
K A
KA
Woodfork
D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D002147:Calmodulin / Q000032:analysis / Q000037:antagonists & inhibitors*; D046508:Culture Techniques; D004351:Drug Resistance; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000032:analysis; D013449:Sulfonamides / Q000494:pharmacology*
D002147:Calmodulin; D007093:Imidazoles; D011960:Receptors, Estrogen; D013449:Sulfonamides; C031938:calmidazolium; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide