Ionic signals in T47D human breast cancer cells

被引:11
作者
Gallagher, JD
Fay, MJ
North, WG
McCann, FV
机构
[1] DARTMOUTH COLL SCH MED,DEPT ANESTHESIOL,LEBANON,NH 03756
[2] DARTMOUTH COLL SCH MED,DEPT PHYSIOL,LEBANON,NH 03756
关键词
ion channels; breast cancer; potassium currents; mitogenic signals;
D O I
10.1016/0898-6568(96)00050-2
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Increasing evidence that ion channels play a key role in the modulation of cellular mitogenesis led us to investigate the membranes of T47D human breast cancer cells to identify the ion currents present. We report here the results of voltage-clamp studies in the whole-cell configuration on isolated, non-synchronized single cells obtained from a ductal breast carcinoma. In these studies we identified an outward rectifying potassium current and a chloride current. The potassium current activated at potentials more positive than -40 mV, reached an average value of 1.4 nA, and did not inactivate with time. This current was sensitive to block by extracellular tetraethylammonium chloride (TEA, IC50 = 1 mu M), was insensitive to charybdotoxin (CTX, IC50 = 7.8 mu M), and was not diminished by repetitive pulses separated by 1 s. Rapid voltage-dependent inactivation of the current was demonstrated by tail current analysis. The current appeared calcium-insensitive. Application of hyperpolarizing pulses did not elicit an inward potassium rectifier current. Treatment with tetrodotoxin did not reveal the presence of an inward sodium current. The potassium current was increased by the presence of aspartate in place of chloride and in the presence of the chloride channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). We conclude that currents present in T47D breast cancer cells include a chloride current and a voltage-gated potassium outward rectifier. We suggest that the potassium current, either alone or in conjunction with potassium currents reported in different human breast cancer cell lines by others, may play a role in the modulation of the cell cycle.
引用
收藏
页码:279 / 284
页数:6
相关论文
共 25 条
[1]   ESTROGENS STIMULATE CELL-PROLIFERATION AND INDUCE SECRETORY PROTEINS IN A HUMAN-BREAST CANCER CELL-LINE (T47D) [J].
CHALBOS, D ;
VIGNON, F ;
KEYDAR, I ;
ROCHEFORT, H .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1982, 55 (02) :276-283
[2]   ROLE OF POTASSIUM CHANNELS IN MITOGENESIS [J].
DUBOIS, JM ;
ROUZAIREDUBOIS, B .
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 1993, 59 (01) :1-21
[3]   INVOLVEMENT OF THE CA-2+-DEPENDENT K+ CHANNEL ACTIVITY IN THE HYPERPOLARIZING RESPONSE INDUCED BY EPIDERMAL GROWTH-FACTOR IN MAMMARY EPITHELIAL-CELLS [J].
ENOMOTO, K ;
COSSU, MF ;
MAENO, T ;
EDWARDS, C ;
OKA, T .
FEBS LETTERS, 1986, 203 (02) :181-184
[4]   1,25-DIHYDROXYVITAMIN D-3 SPECIFICALLY BINDS TO A HUMAN-BREAST CANCER CELL-LINE (T47D) AND STIMULATES GROWTH [J].
FREAKE, HC ;
MARCOCCI, C ;
IWASAKI, J ;
MACINTYRE, I .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1981, 101 (04) :1131-1138
[5]   MERCURY SUPPRESSION OF A POTASSIUM CURRENT IN HUMAN B-LYMPHOCYTES [J].
GALLAGHER, JD ;
NOELLE, RJ ;
MCCANN, FV .
CELLULAR SIGNALLING, 1995, 7 (01) :31-38
[6]   CHARYBDOTOXIN AND ITS EFFECTS ON POTASSIUM CHANNELS [J].
GARCIA, ML ;
KNAUS, HG ;
MUNUJOS, P ;
SLAUGHTER, RS ;
KACZOROWSKI, GJ .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1995, 269 (01) :C1-C10
[7]  
GRAHAM ML, 1990, CANCER RES, V50, P6208
[8]  
HORWITZ KB, 1978, CANCER RES, V38, P2434
[9]   VARIANT T47D HUMAN-BREAST CANCER-CELLS WITH HIGH PROGESTERONE-RECEPTOR LEVELS DESPITE ESTROGEN AND ANTI-ESTROGEN RESISTANCE [J].
HORWITZ, KB ;
MOCKUS, MB ;
LESSEY, BA .
CELL, 1982, 28 (03) :633-642
[10]   ESTABLISHMENT AND CHARACTERIZATION OF A CELL-LINE OF HUMAN-BREAST CARCINOMA ORIGIN [J].
KEYDAR, I ;
CHEN, L ;
KARBY, S ;
WEISS, FR ;
DELAREA, J ;
RADU, M ;
CHAITCIK, S ;
BRENNER, HJ .
EUROPEAN JOURNAL OF CANCER, 1979, 15 (05) :659-670