Establishment of two hormone-responsive mouse mammary carcinoma cell lines derived from a metastatic mammary tumor.
We report the establishment of two mouse mammary cancer cell lines, MC7-2A and MC7-2B obtained from a mouse mammary carcinoma induced by medroxyprogesterone acetate (MPA) and maintained by syngeneic transplantation in BALB/c mice. They are epithelial (express cytokeratins) and express both estrogen receptors alpha (ERalpha) and progesterone receptors (PRs) isoforms A and B (western blots). In vitro, MPA inhibited 3H-thymidine uptake, starting from concentrations as low as 10(-13) M in MC7-2A and 10(10) M in MC7-2B; the antiprogestin RU 486 exerted a stimulatory effect at 10(-14) M in both cell lines; 17-beta-estradiol (E2) also exerted a stimulatory effect starting at 10(-10) M in MC7-2A and at 10(-13) M in MC7-2B. When transplanted in syngeneic mice, both cell lines originated adenocarcinomas that gave rise to lung metastases within 3 months. In in vivo studies, in MC7-2A, the antiprogestin inhibited completely tumor growth, E2 induced a slight although significant ( p < 0.05) stimulatory effect and MPA stimulated tumor growth while MC7-2B cells were unresponsive to all treatments. ER and PR were also expressed in tumors as assessed by immunohistochemistry. Two marker chromosomes were identified by FISH as translocations between chromosomes 4 and 7, and between chromosomes X and 2; the third marker chromosome remains unidentified. All these markers were also present in the parental tumor. A new marker, a centric fusion of chromosomes 2, was acquired in both cell lines. Considering that there are very few murine breast carcinoma responsive cell lines, these cells represent new tools in which the regulatory effect of hormones can be studied.
Efeyan
Alejo
A
Laboratory of Hormonal Carcinogenesis, Instituto de Biología y Medicina Experimental - Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Fabris
Victoria
V
Merani
Susana
S
Lanari
Claudia
C
Molinolo
Alfredo A
AA
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015153:Blotting, Western; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000556:secondary / Q000662:veterinary; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000032:analysis / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D005819:Genetic Markers; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate