Deregulation of c-myc gene expression in human colon carcinoma is not accompanied by amplification or rearrangement of the gene.

Abstract

The structure and expression of the c-myc oncogene were examined in 29 primary human colon adenocarcinomas. Dot blot hybridization of total RNA showed that 21 tumors (72%) had considerably elevated expression of c-myc (5-to 40-fold) relative to normal colonic mucosa. These data were corroborated by Northern blots of polyadenylated RNA, which showed a 2.3-kilobase transcript. Southern analysis of the c-myc locus in these tumors indicated the absence of amplification or DNA rearrangement in a 35-kilobase region encompassing the gene. In a parallel study, elevated expression of c-myc without amplification or DNA rearrangement was also observed in three of six colon carcinoma cell lines examined; in addition, unlike a normal colon cell line control, these three cell lines exhibited constitutive, high-level expression of the gene during their growth in cultures. These results indicate that elevated expression of the c-myc oncogene occurs frequently in primary human colon carcinomas and that the mechanism involved in the regulation of c-myc expression is altered in tumor-derived cell lines.

c-MYC Activation in Primary and Metastatic Ductal Adenocarcinoma of the Pancreas: Incidence, Mechanisms, and Clinical Significance

“…Although numbers are too low to allow conclusions, these findings suggest that at least in some pancreatic cancers, c-MYC alterations occur in preinvasive stages of tumor development. Reports on c-MYC deregulation in premalignant lesions of the bladder and colon (23)(24)(25) are in support of our findings. In this study, activation of c-MYC (either by gene amplification or protein overexpression) was found less frequently in lymph node metastases as compared with primary pancreatic tumors, and it did not correlate with either tumor stage or tumor size.…”

“…Discrepancy between c-MYC gene amplification and protein overexpression has also been described in bladder and colon cancers. It was therefore concluded that c-MYC amplification represents only one of multiple possible mechanisms leading to enhanced protein expression in various neoplasias (20,(23)(24)(25). Overall, the functional aspects of c-MYC gene amplification and protein overexpression remain unknown.…”

Apoptosis-prone phenotype of human colon carcinoma cells with a high level amplification of the c-myc gene

“…It is known that colon carcinomas are very resistant to drugs commonly used in chemotherapy (Endicott and Ling, 1989) and that a high level of ampli®cation of c-myc is rare in these tumors (Erisman et al, 1985). Actually, a recent report indicates that a fraction of colon carcinomas is characterized by c-myc gene ampli®cation (mainly at a low level) and that this may predispose patients to a better response to treatment (Augenlicht et al, 1997).…”

MYC oncogenes and human neoplastic disease

“…Numerous subsequent reports have provided con®rmation of this ®nding at both the mRNA and protein level in both cell lines and primary tumors (Erisman et al, 1988;Finley et al, 1989;Rochlitz et al, 1996;Stewart et al, 1986;Yang et al, 1996). Although the original report by Erisman et al (1985) reported that the C-MYC gene was not ampli®ed in tumors, several subsequent studies have provided evidence for low-level ampli®cation (2 ± 5-fold) in about one-third of tumors (Finley et al, 1989;Rochlitz et al, 1996;Augenlicht et al, 1997;Masramon et al, 1998). However, this does not explain the disproportionate increase in c-myc expression in the vast majority of tumors.…”