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The mRNA of L-type calcium channel elevated in colon cancer: protein distribution in normal and cancerous colon.

ABSTRACT: Previous reports indicate that the mRNA for the cardiac isoform of the voltage-gated L-type calcium channel (alpha(1C)) is elevated in colon cancer. The aim of these experiments was to verify that the mRNA for alpha(1C) was significantly increased in tumors of two separate populations of patients when compared to normal adjacent mucosa. The second aim was to measure the distribution of alpha(1C) using immunocytochemistry in normal human colon and in colon cancer and to determine what might regulate the channel expression. Biopsies were taken from patients with various stages of colon cancer and nearby normal mucosa were used as control. RNA was prepared and mRNA level measured by semiquantitative reverse transcriptase-polymerase chain reaction. The mRNA of the calcium channel was compared with other markers including beta-actin. The mRNA for alpha(1C) was increased significantly in colon cancers compared to nearby adjacent mucosa. Using confocal microscopy alpha(1C) was localized mainly at the apical membrane in the surface epithelium of normal human colon with less distribution on the lateral and basal membranes. The channel was localized on the lateral and basal membranes in crypt cells. Calcium channel localization appeared to be nearer nuclei in colon cancer samples, in part because of the smaller size of the cells. Likewise, cultured Caco-2 and T84 cells showed a membrane distribution. Western blotting indicated that alpha(1C) protein was increased in nonconfluent cultures of colonic carcinoma cells compared to confluent cells and immunocytochemistry confirms that there is more calcium channel protein in cells that are nonconfluent. We conclude that the increase in mRNA of alpha(1) subunit of the cardiac isoform of the L-type calcium channel may be a useful marker of colon cancer compared to other markers because the increase is large and this increase can be documented on small samples using a simple semiquantitative reverse transcriptase-polymerase chain reaction. We found that alpha(1C) protein is increased when colonic cells are nonconfluent or dividing which may account for the increase in cancer.

SUBMITTER: Wang XT

PROVIDER: S-EPMC1885745 | biostudies-literature | 2000 Nov

REPOSITORIES: biostudies-literature

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The mRNA of L-type calcium channel elevated in colon cancer: protein distribution in normal and cancerous colon.

Wang X T XT Nagaba Y Y Cross H S HS Wrba F F Zhang L L Guggino S E SE

The American journal of pathology 20001101 5

Previous reports indicate that the mRNA for the cardiac isoform of the voltage-gated L-type calcium channel (alpha(1C)) is elevated in colon cancer. The aim of these experiments was to verify that the mRNA for alpha(1C) was significantly increased in tumors of two separate populations of patients when compared to normal adjacent mucosa. The second aim was to measure the distribution of alpha(1C) using immunocytochemistry in normal human colon and in colon cancer and to determine what might regul ...[more]

PMID: 11073814

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Project description:Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) is a regulator of the female reproductive system, an indicator of ovarian reserve and a growth inhibitor of Müllerian duct-derived tumors in vivo and in vitro. The objective of the present study was to analyze MIS/AMH type II receptor (MIS/AMHRII) protein and mRNA expression in healthy human endometria compared with patients with endometrial hyperplasia and endometrial cancer, providing a foundation for MIS/AMH as a biological modifier for treatment of endometrial hyperplasia and endometrial cancer. The present study included healthy endometrial tissues (n=20), simple endometrial hyperplasia tissues without atypia (n=17), complex endometrial hyperplasia tissues without atypia (n=24) and endometrial cancer tissues (n=8). The location and variation of MIS/AMHRII protein expression was observed by immunohistochemistry. The expression was graded by two pathologists and was categorized as follows: Negative, weakly positive, moderately positive or strongly positive. Reverse transcription-quantitative polymerase chain reaction was used to quantify MIS/AMHRII mRNA expression. The expression of MIS/AMHRII protein was observed in the cytoplasm of healthy human endometria, endometrial hyperplasia and endometrial cancer cells. The frequency of MIS/AMHRII protein expression was 20.22±10.35% in the proliferative phase of the healthy endometrium and 24.09±11.73% in the secretory phase of the healthy endometrium. However, no differences were observed in the menstrual cycle phases. The frequency was 54.50±16.59% in endometrial hyperplasia without atypia, 55.10±15.87% in endometrial hyperplasia with atypia and 73.88±15.70% in endometrial cancer, indicating that expression was enhanced as the disease progressed from healthy to malignant status. In endometrial hyperplasia, MIS/AMHRII protein expression was significantly associated with histological complexity compared with atypia status. The present study demonstrated that MIS/AMHRII is present in healthy endometria, endometrial hyperplasia and endometrial cancer. The low expression frequency of MIS/AMHRII was not significantly different among normal endometrial tissues, however, the protein expression was elevated in endometrial hyperplasia and endometrial cancer. These findings indicated that the study of bioactive MIS/AMH, as a possible treatment for tumors expressing the MIS/AMH receptor, is essential.

Dataset Information

The mRNA of L-type calcium channel elevated in colon cancer: protein distribution in normal and cancerous colon.

Publications

The mRNA of L-type calcium channel elevated in colon cancer: protein distribution in normal and cancerous colon.

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