Alterations in the tumor suppressor genesp53, RB, p16/MTS1, andp15/MTS2 in human pancreatic cancer and hepatoma cell lines

Abstract

The tumor suppressor genes p53, retinoblastoma (RB), p16, and p15 encode proteins that regulate the cell cycle cooperatively by controlling the transition from G1 to S phase and may play an important role in cell growth and differentiation. To screen for abnormalities in these genes in cancer, we performed genetic analysis in six human pancreatic cancer and five hepatoma cell lines, by single-strand conformation polymorphism (SSCP) analysis, direct sequencing, and the reverse transcriptase-polymerase chain reaction (RT-PCR). All six pancreatic cancer cell lines had p53 mutations, with the concomitant loss of the other normal allele, encoding wild-type p53. Frequent homozygous deletions were found in p16 and p15, but the RB gene was expressed. Four of the five hepatoma cell lines had p53 mutations with loss of the normal allele and aberrant RB. There were no deletions of p16 and p15 in any of the hepatoma cell lines. These findings suggest that alterations in the p53, p16, and p15 genes are common in human pancreatic cancer cell lines, while p53 or RB mutations are common in hepatoma cell lines. Alterations of these tumor suppressor genes may thus be important features in organ-specific carcinogenesis.

Fluorine-18 Fluorodeoxyglucose Uptake in Hepatocellular Carcinoma: Correlation with Glucose Transporters and p53 Expression

“…18 Thus, it was found out that the HuH7 cell line is the one that has the greatest expression of this protein, followed by the HepG2 cells. It was confirmed the absence of p53 expression by the Hep3B2.…”

“…It was found that not always GLUT1 and GLUT3 are the most expressed by these cell lines. Conclusions: Our results shown that the p53 expression influences [ 18 H epatocellular Carcinoma (HCC) is one of most lethal cancers, with an increasing incidence in several regions of the world. Without specific treatment, the prognosis is very poor and survival is not prolonged.…”

“…According to the literature these cell lines differ in p53 expression, HepG2 cells express normal P53 (wp53), HuH7 and Hep3B2.1-7 express different mutated forms of p53 (mp53), thus, the HuH7 cell line overexpress p53 and Hep3B2.1-7 don't express this protein. 18 Cells were propagated on adherent cultures in Dulbecco's Modified Eagle Medium (DMEM) with 10% Fetal Bovine Serum (FBS) (Gibco 2010-09), 100 units/ml of penicillin and 100 mg/ml of streptomycin (Gibco 15140-122), pH 7.4 and incubated at 37 8C in 5% CO 2 atmosphere. We used two different formulation of DMEM medium with high glucose (HG) (25 mM) (Sigma D5648) and with low glucose (LG) (5 mM) (Gibco 31600-091), in order to clarify the influence of the glucose concentration on [ 18 F]FDG uptake and in the expression of GLUTs.…”

“…It was found out that for all cell lines, [ 18 F]FDG uptake is higher when cells grow in low glucose medium, however, the glucose level doesn't affect mostly the GLUTs expression. The Hep3B2.1-7 (p53null) is always the one that have higher [ 18 F]FDG uptake. It was found that not always GLUT1 and GLUT3 are the most expressed by these cell lines.…”

“…7 Although this imaging technique is not widely used for liver tumors, recent studies have shown that PET enables the identification of different uptake profiles in tumors of the same organ, namely HCC, but with different genetic profiles, which indicates that PET can be used in the diagnosis of liver cancers, leading the patients to a more personalized therapies. [8][9][10] Increased [ 18 11,12 GLUT1 and GLUT3 were originally identified as glucose transporters with primary role in the transport of [ 18 F] FDG, since it is known that these transporters are overexpressed in tumor cells. However, more recently, GLUT5 and GLUT12 also appeared as transporters with an active role in this process, in particular in breast cancer cells.…”