Drug-induced biochemical markers of cancer in cervical carcinoma cells.
The elevation in the serum level of CEA in cancer patients undergoing treatment with 5-FU and other antitumor drugs has been reported. In the present study, the ectopic synthesis of multiple carcinoplacental markers has been observed to be induced (10- to 264-fold) simultaneously in the same cervical carcinoma cells (HeLa65, HeLa71 and HeLa2.2) by hydroxyurea and sodium butyrate. Among the drug-induced biochemical markers observed in HeLa cells are four sialopeptides. Regan Isoenzyme (Placental Isoenzyme of Alkaline Phosphatase), HCT-Beta, FSH-Beta, HCG-Alpha and also a steroid hormone, Progesterone. The peptide and steroid hormones were quantitated by specific radioimmunoassays (RIA), in cultured cells, media, and homogenates of tumor tissues. The induction of biochemical markers was observed also with lung carcinoma cells. That multiple polypeptides, or steroids regulated by them, are simultaneously inducible in the same cancer cells, suggest the proximity on the DNA strand of several oncofetal and oncoplacental genes derepressed by antineoplastic drugs. This fundamental study has had important clinical ramifications. The results may be used to recognize the retention by cancer patients of occult malignancy after radiotherapy or surgery. The unsuspected metastasis may be reflected by a transient rise in the serum level of these markers during chemotherapy with anticancer drugs, which specifically inhibit DNA replication without interfering with the transcription of messenger-RNA and subsequent translation of proteins. The drug-induced protein-hormones, observed in this study, are the products of activated trophoblastic/pituitary genes in the nondividing DNA of neoplastic cells.
D000469:Alkaline Phosphatase; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis; D006063:Chorionic Gonadotropin / Q000096:biosynthesis / Q000378:metabolism; D018997:Chorionic Gonadotropin, beta Subunit, Human; D005260:Female; D005640:Follicle Stimulating Hormone / Q000096:biosynthesis; D058851:GPI-Linked Proteins; D015292:Glycoprotein Hormones, alpha Subunit; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D006828:Hydatidiform Mole / Q000378:metabolism; D006918:Hydroxyurea / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000378:metabolism; D010446:Peptide Fragments / Q000096:biosynthesis / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
D002087:Butyrates; D002272:Carcinoembryonic Antigen; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D058851:GPI-Linked Proteins; D015292:Glycoprotein Hormones, alpha Subunit; D007527:Isoenzymes; D010446:Peptide Fragments; D020148:Butyric Acid; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D000469:Alkaline Phosphatase; C019839:alkaline phosphatase, placental; D006918:Hydroxyurea