Tropomyosins of human mammary epithelial cells: consistent defects of expression in mammary carcinoma cell lines.
Suppression of synthesis of specific tropomyosin (TM) isoforms occurs commonly in human, murine, and avian fibroblasts transformed by retroviral oncogenes or other modalities. The resulting deficiency or altered distribution of TMs may predispose the cells to microfilament instability and contribute to expression of the transformed phenotype. In this study we have asked whether defects in TM expression had relevance to human neoplasia, which arises most often in cells of the epithelial lineage rather than in fibroblasts and often is unrelated to demonstrable expression of oncogenes. TMs were characterized in normal primary human mammary epithelial cells (HMEC) and in an immortalized nontumorigenic cell line derived from them. Seven TM isoforms were identified in primary HMEC, two of which may be unique to epithelial cells. Immortalized nontumorigenic HMEC expressed the same array of isoforms. Of six established human breast carcinoma cell lines studied, all failed to express the Mr 39,000 TM isoform and five of six also lacked expression of either the Mr 38,000 or 35,000 isoform. Northern blot analysis with probes specific for the 1.1-kilobase mRNA of fibroblast TM1 detected a mRNA of this size in normal HMEC. This mRNA, which probably encodes the Mr 39,000 TM missing from all the carcinoma lines, was absent from five of the six breast cancer cell lines. These results indicate that abnormalities in TM expression in neoplastic cells are not limited to fibroblasts. The high frequency and consistent nature of such abnormalities among cell lines derived from human breast cancer raises the possibility that such abnormalities in expression of a major cytoskeletal protein may play a role in human neoplasia.
Bhattacharya
B
B
Cell and Molecular Physiology Section, National Cancer Institute, Bethesda, Maryland 20892.
Prasad
G L
GL
Valverius
E M
EM
Salomon
D S
DS
Cooper
H L
HL
D000199:Actins / Q000378:metabolism; D015152:Blotting, Northern; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D015180:Electrophoresis, Gel, Two-Dimensional; D004848:Epithelium / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D007526:Isoelectric Point; D008970:Molecular Weight; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000235:genetics; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D012333:RNA, Messenger; D014335:Tropomyosin