c-myc amplification and enhancement of sensitivity to cytosine arabinoside: an in vitro and in vivo study on four sublines established from a pulmonary adenocarcinoma.
OBJECTIVE
Meticulous treatment strategies taking tumor heterogeneity into account are considered essential to achieve breakthroughs in current cancer therapy. We analyzed tumor heterogeneity in the primary tumor of a patient with pulmonary adenocarcinoma characterized by a poor prognosis.


METHODS
Four sublines with different growth characteristics in vitro were established from the tumor using a method for short-term selective cultivation. We examined the differences in morphological, biochemical, and genetic findings of these sublines.


RESULTS
Differences in the histological features of the transplanted tumors were seen in the four sublines. The 88-2T and 88-2 tumors revealed a well-differentiated adenocarcinoma; the 88-2F tumor revealed a large cell-like carcinoma resembling the metastatic tumor in the lymph nodes; and the 88-2FA tumor was composed of signet-ring cells. There were differences in oncogenes, with the 88-2F line alone exhibiting 12-fold amplification of c-myc. Sensitivity to cytosine arabinoside (Ara C) was specifically increased in the 88-2F cell line, alone.


CONCLUSIONS
These sublines demonstrate that human pulmonary adenocarcinoma has various types of heterogeneity within the primary tumor. Furthermore, c-myc amplification may play an important role in altering phenotype and growth characteristics in vitro and in vivo, and for increasing sensitivity to Ara C and the potential of cancer cells to metastasize to lymph nodes.
Department of Surgery, Semine Hospital, 55-2 Tominegishi, Semine-cho, Kurihara-gun, Miyagi 989-4501, Japan.
Shunsuke
S
Kobayashi
Masashi
M
Noda
Katuhiko
K
Isogami
Toru
T
Hasumi
D000230:Adenocarcinoma / Q000473:pathology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002455:Cell Division; D003561:Cytarabine / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005784:Gene Amplification; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010641:Phenotype; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine